Background: Essential tremor (ET) is one of the most prevalent movement disorders. However, the complete understanding of ET pathophysiology remains elusive. Objective: To explore the pathophysiological role of primary motor cortex (M1) in ET, specifically exploring its neurophysiological changes and their correlation with voluntary motor abnormalities. Methods: We recruited 30 ET patients and 18 healthy controls (HC). Evaluations were conducted on patients using clinical scales. Transcranial magnetic stimulation (TMS) was used to assess M1 excitability, including motor thresholds and motor evoked potentials (MEPs) input/output curve, together with intracortical excitability measures. Long‐term potentiation (LTP)‐like plasticity of M1 was tested using intermittent theta‐burst stimulation (iTBS). Objective assessments of tremor and voluntary movement execution during finger‐tapping were conducted through kinematic analysis. Finally, we explored the potential relationship between TMS, clinical, and kinematic data. Results: Compared with HC, ET patients had lower excitability, intracortical inhibition, and lower LTP‐like plasticity of M1. ET patients also exhibited slower finger‐tapping performance compared with HC. Among ET patients, the degree of movement slowing during finger‐tapping correlated with alterations in corticospinal excitability. Specifically, reduced M1 excitability was associated with lower finger‐tapping velocity. No other correlations were found. Conclusions: The study findings reveal neurophysiological alterations of M1 in ET and demonstrate correlations between excitability measures and voluntary motor performance. These results provide novel insight into the pathophysiology of ET, emphasizing the role of M1 changes in this condition. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background: In spite of being considered the gold-standard of care, little is known about the real-life use of inhome and multidisciplinary care in atypical parkinsonism. Objective: Primary: Examine real-life multidisciplinary care use for Progressive Supranuclear Palsy (PSP). Secondary: a) Compare PSP care to advanced Parkinson's disease (APD) care; (b) Explore demographic and clinical variables associated with care needs in both groups. Methods: A cross-sectional multicenter observational study enrolled 129 PSP patients and 65 APD patients (Hoehn and Yahr >= 3), matched for sex and age. Univariate and multivariate regression analysis were performed. Results: Over the previous year, 40 % of PSP patients did not encounter a physical therapist, while only one-third met a speech and language therapist and 5 % an occupational therapist. More than 20 % received in-home care and 32 % needed home structural changes. Compared to APD, PSP patients required more day-time, night-time and home structural changes. When considering both PSP and APD in multivariate analysis, reduced functional autonomy and living without a family caregiver were both related to day-time home assistance and to the need of at least one home care service. A PSP diagnosis compared to APD was a risk factor for having at least four multidisciplinary visits in a year. Finally, PSP diagnosis and being from the Northern Italy were significantly related with home structural changes. Conclusions: There's a significant gap in providing multidisciplinary care for PSP patients. Our findings emphasize the need for a shared, integrated care plan at a national level for patients with atypical parkinsonism.

Heterozygous mutations in the GBA1 gene, encoding the enzyme glucocerebrosidase (GCase), are major risk factors for Parkinson’s Disease (PD). Ambroxol, a small chaperone originally used as a mucolytic agent, has been shown to cross the blood–brain barrier, enhance GCase activity, and reduce α-synuclein levels, making it a promising therapeutic candidate for disease-modifying effects in GBA1-associated PD (GBA1-PD). This study aimed to develop a method to quantify ambroxol levels in human plasma and cerebrospinal fluid (CSF) using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Ambroxol was determined by online solid-phase extraction (SPE), coupled with LC-MS/MS, by gradient elution on a monolithic column. Detection employed a 3200 QTRAP tandem mass spectrometer in the positive electrospray ionization mode. Calibration curves exhibited linearity across the analyzed ranges in both plasma and CSF. The recovery rate ranged from 106.7% to 113.5% in plasma and from 99.0% to 103.0% in CSF. No significant matrix effect was observed. Intra-day and inter-day precisions were below 11.8% in both matrices, and accuracy ranged from 89.9% to 103.1% in plasma and from 96.3% to 107.8% in CSF. We evaluated and confirmed the stability of the analyte in plasma and CSF across various storage conditions. The method was successfully validated according to European Medicine Agency (EMA) guidelines and its applicability was confirmed in the context of a multicenter, randomized, double-blind, placebo-controlled, phase II study, designed to monitor the ambroxol levels in the plasma and CSF of GBA1-PD.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), unlike pediatric acute-onset neuropsychiatric syndrome (PANS), is triggered by infections. This study aimed to assess the differences in low-grade endotoxemia and oxidative stress between these conditions. A cross-sectional study compared serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes, lipopolysaccharide (LPS), and zonulin in 30 PANDAS, 21 PANS, and 30 control (CT) children matched for age and gender. Zonulin was used to assess gut permeability. Patients with PANDAS showed significantly higher serum levels of sNOX2-dp, isoprostanes, LPS, and zonulin than PANS and controls, while no significant differences were found between PANS and controls. sNOX2-dp correlated with isoprostanes (Rs = 0.708; p < 0.001), LPS (Rs = 0.584; p < 0.001), and zonulin (Rs = 0.662; p < 0.001). Multiple regression identified isoprostanes (β = 0.599; p < 0.001) and zonulin (β = 0.295; p = 0.01) as independent predictors of sNOX2-dp (R² = 81%). PANDAS and PANS showed distinct profiles of LPS, zonulin, NOX2, and isoprostanes. Future research should explore therapies targeting endotoxemia and oxidative stress for potential clinical benefits.

Background: Task‐specific orofacial tremor is a rare condition in which rhythmic oscillations of orofacial muscles occur during specific actions. Drinking tremor represents a recurrent pattern in isolated reports, although its phenomenology and underlying mechanisms remain incompletely defined. Cases: We report three cases of orofacial drinking tremor, each showing a different pattern. Differences involved the distribution of orofacial muscle activity and the presence of additional signs, including tremor in other body regions or subtle dystonic postures. Variability in task dependence, posture sensitivity, and sensory modulation contributed to the heterogeneity of these presentations. Literature Review: Published reports describe a spectrum of orofacial drinking tremors, ranging from strictly task‐specific patterns to mixed task‐ and position‐dependent presentations. Some patients exhibit subtle dystonic features, whereas others show no clear additional neurological signs. Electrophysiology typically demonstrates regular 5–8 Hz rhythmic discharges in the orofacial muscles. Systemic pharmacological therapies offer limited benefit, whereas botulinum toxin remains the most effective option. Conclusions: Current evidence suggests that orofacial drinking tremor does not represent a single clinical entity. An approach integrating detailed phenomenological characterization with plausible pathophysiological mechanisms may improve diagnostic interpretation and guide individualized management strategies.