Distinctive cognitive phenotypes in Parkinson's disease patients with GBA mutations and without dementia: a multicentre cross-sectional retrospective study.

Background: Cognitive impairment is a major non-motor complication of Parkinson's disease (PD). GBA mutations are associated with an increased risk, with PD-GBA+ patients typically showing earlier disease onset and faster cognitive decline. However, the specific cognitive phenotype of these patients remains unclear.

Effects of GBA1 Variants in Patients With Parkinson's Disease and Levodopa-Carbidopa Intestinal Gel: A Nation-Wide, Multicenter, Longitudinal, "Real-World" Study. The EPIC Study.

Background: The outcome of levodopa/carbidopa intestinal gel (LCIG) in Parkinson's disease carriers of GBA1 mutations (GBA-PD) remains uncertain.

Objective: To evaluate the safety and efficacy of LCIG in a large PD cohort, focusing on GBA1 variants.

Methods: This multicenter, retrospective, longitudinal "real-world" study included consecutive patients with advanced PD treated with LCIG at 31 Italian centers; data were collected at baseline, 1-, 5-year, and last-available follow-up.

Subthalamic beta power and gait in Parkinson's disease during unsupervised remote monitoring.

Background: Brain-sense enabled deep brain stimulation (DBS) in Parkinson's disease (PD) allows understanding the neurophysiological role of basal ganglia in gait dysfunction. Subthalamic nucleus (STN) local field potentials (LFPs) indicate pathological PD gait changes, but previous evidence is based on data obtained in controlled settings. This study aims to examine the relationship between STN oscillations and sensor-derived gait parameters in PD, in an unsupervised, real-life environment.

Long-term infective complications of deep brain stimulation in Parkinson's disease: A 22-year follow-up.

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD), but infections remain a significant concern. This study evaluated infection rates and their impact in PD patients who underwent subthalamic nucleus (STN)-DBS over a 23-year period.

Methods: A total of 172 PD patients who underwent bilateral STN-DBS between 2000 and 2023 were included in this retrospective study.

Identification of Novel Mutations in Patients Affected by Gaucher Disease.

Gaucher disease is an autosomal recessive disorder caused by dysfunction of the enzyme glucocerebrosidase. The enzyme deficiency is mainly due to mutations in the gene, and it is responsible for the accumulation of glucosylceramide within the lysosomes of monocyte macrophage-derived cells; causing the associated symptomatology. In this paper, we describe six new mutations identified in the gene, which, in combination with other mutations already documented, lead to absent or reduced glucocerebrosidase activity, resulting in pathological accumulation of the specific substrate and the clinical manifestations associated with Gaucher disease.

Changes in the thalamocortical component of high frequency oscillations following botulinum toxin treatment in cervical dystonia.

Objective: This study aims to investigate the central effects of Botulinum toxin type A (BoNT-A) on the somatosensory system in patients with cervical dystonia (CD), focusing on the thalamocortical pathway using high-frequency oscillations (HFOs) and short-latency afferent inhibition (SAI).

Methods: An observational longitudinal study was conducted on 10CD patients and 10 healthy controls (HC). HFOs and SAI were assessed for CD and HC at baseline (T0; the day before BoNT-A treatment).

1953-2023. Seventy Years of the Nerve Growth Factor: A Potential Novel Treatment in Neurological Diseases?

Rita Levi-Montalcini's 1953 discovery of nerve growth factor (NGF) in mouse sarcoma tumors marked a groundbreaking moment in neuroscience. NGF, a key signaling molecule, became the first identified neurotrophic factor, influencing the growth, differentiation, and survival of neurons in both peripheral and central nervous systems. NGF and related neurotrophic factors hold therapeutic potential for various neurological disorders, such as Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, amyotrophic lateral sclerosis, spinal cord injuries, neuropathies, traumatic brain injuries, and stroke.

Deep brain stimulation in Parkinson's disease: a comparison of accuracy and clinical outcomes of frame-based, frameless and frameless fiducial-less techniques.

Background: The effectiveness of deep brain stimulation (DBS) for Parkinson's disease (PD) depends on implantation accuracy. DBS initially employed a stereotactic frame (frame-based, FB), but technological advancements led to the development of less invasive methods based on fiducial markers (F + F) or intraoperative imaging (F-F). This study compares the accuracy and efficacy of three DBS-STN implantation techniques.

Fear of falling impairs spatiotemporal gait parameters, mobility, and quality of life in Parkinson's disease: a cross-sectional study.

Background: Fear of Falling (FOF) significantly affects Parkinson's Disease (PD) patients by limiting daily activities and reducing quality of life (QoL). Though common in PD, the relation between FOF, mobility, and QoL remains unclear. This study examines the connections between FOF, gait, daily motor activity, and QoL in PD patients.

The effects of transcutaneous auricular vagus nerve stimulation (taVNS) on cholinergic neural networks in humans: A neurophysiological study.

Objective: The mechanisms of actions of transcutaneous auricular vagus nerve stimulation (taVNS) are still unclear, however the activity of the cholinergic system seems to be critical for the induction of VNS-mediated plasticity. Transcranial Magnetic Stimulation (TMS) is a well-suited, non-invasive tool to investigate cortical microcircuits involving different neurotransmitters. Herein, we evaluated the effect of taVNS on short-latency afferent inhibition (SAI), a TMS paradigm specifically measuring cholinergic neurotransmission.

Driving Abilities and Wearing-Off in Parkinson's Disease: A Driving Simulation Study.

Background/objectives: Driving abilities require the synchronized activity of cerebral networks associated with sensorimotor integration, motricity, and executive functions. Drivers with Parkinson's disease (DwP) have impaired driving ability, but little is known about the impact of "wearing-off" and therapies in addition to L-DOPA on driving capacities. This study aimed to (i) compare driving performance between DwP during different motor states and healthy controls and (ii) assess the impact of add-on therapies on driving abilities.

Investigating the Impact of the Parkinson's-Associated GBA1 E326K Mutation on β-Glucocerebrosidase Dimerization and Interactome Dynamics Through an In Silico Approach.

Heterozygous mutations or genetic variants in the gene, which encodes for the β-glucocerebrosidase (GCase), a lysosomal hydrolase enzyme, may increase the risk of Parkinson's disease (PD) onset. The heterozygous E326K form is one of the most common genetic risk factors for PD worldwide, but, to date, the underlying molecular mechanisms remain unclear. Here, we investigate the effect of the E326K on the structure, stability, dimerization process, and interaction mode with some proteins of the interactome of GCase using multiple molecular dynamics (MD) simulations at pH 5.

Immunometabolic Signature and Tauopathy Markers in Blood Cells of Progressive Supranuclear Palsy.

Background: Peripheral immune cells critically contribute to the clinical-pathological progression of neurodegenerative diseases and also represent a reliable frame for translational applications. However, data on progressive supranuclear palsy (PSP) are almost scarce in this regard.

Objective: Our goal is to provide a broad biological characterization of peripheral immune cells in a selected PSP cohort.

Body image appearance in Parkinson's disease patients on device aided therapies.

Introduction: Parkinson's disease patients may experience altered body image perception. Advanced Parkinson's disease (aPD) with motor complications often requires surgical and device-aided treatments (DAT), such as levodopa-carbidopa intestinal gel (LCIG) and deep brain stimulation (DBS). Understanding body image perception is crucial when managing these devices.

Comprehensive Observational and Longitudinal study on the Outbreak of Stroke-related Spasticity focusing on the Early Onset management with Botulinum NeuroToxin (COLOSSEO-BoNT): protocol for a real-world prospective observational study on upper limb spasticity.

Introduction: Poststroke spasticity (PSS) affects up to 40% of patients who had a stroke. Botulinum neurotoxin type A (BoNT-A) has been shown to improve spasticity, but the optimal timing of its application remains unclear. While several predictors of upper limb PSS are known, their utility in clinical practice in relation to BoNT-A treatment has yet to be fully elucidated.

The influence of sex on non-motor wearing-off in Parkinson's disease: A WORK-PD post-hoc study.

Introduction: The wearing-off phenomenon is characterized by the recurrence of motor and non-motor symptoms of Parkinsonism during a period free from levodopa. It is a pivotal aspect marking the end of the pharmacological "honeymoon" period in Parkinson's disease (PD). A growing body of literature is connecting sex with the likelihood of developing fluctuations.

Production of an induced pluripotent stem cell line CSSi018-A (14192) from a patient with hypomyelinating leukodystrophy 7 (HLD7) carrying biallelic variants of POLR3A (c.1802 T > A; c.4072G > A).

Hypomyelinating leukodystrophies (HLD) are a group of heterogeneous genetic disorders characterized by a deficit in myelin deposition during brain development. Specifically, 4H-Leukodystrophy is a recessive disease due to biallelic mutations in the POLR3A gene, which encodes one of the subunits forming the catalytic core of RNA polymerase III (PolIII). The disease also presents non-neurological signs such as hypodontia and hypogonadotropic hypogonadism.

Increased glucosylsphingosine levels and Gaucher disease in GBA1-associated Parkinson's disease.

Introduction: Gaucher's disease (GD) is caused by biallelic mutations in the GBA1 gene, leading to reduced glucocerebrosidase (GCase) activity and substrate (glucosylceramide and glucosylsphingosine, GlcSph) accumulation. GBA1 variant carriers are at risk of Parkinson's disease (PD), but only those with biallelic mutations cross the threshold of GCase reduction, leading to substrate accumulation and GD. The link between GBA1 mutations, GD and PD is not fully understood.

Combining conventional and smartphone technologies to evaluate the psychomotor status in chronic malnutrition: A cross-sectional pilot study in sub-Saharan Africa.

Malnutrition remains a pressing health concern in developing nations, contributing to growth delay (stunting) and psychomotor impairments among the youth. Tanzania has the highest prevalence of stunting, yet the psychomotor status of its population has not been previously studied. To address this gap, we gathered anthropometric, nutritional, and psychomotor data from 211 children with the aim of assessing the reliability of digital tools as indicators of psychomotor performance in relation to the nutritional status.

The chronic use of serotonin norepinephrine reuptake inhibitors facilitates dyskinesia priming in early Parkinson's disease.

Background: Parkinson's disease (PD) patients are frequently exposed to antidepressant medications (ADMs). Norepinephrine (NE) and serotonin (5HT) systems have a role in levodopa-induced dyskinesias (LID) pathophysiology.

Methods: We performed a longitudinal analysis on the PPMI cohort including drug-naïve PD patients, who are progressively exposed to dopamine replacement therapies (DRTs) to test the effect of ADM exposure on LID development by the 4th year of follow-up.

Emotional atypical arousal ratings for unpleasant stimuli in patients with Parkinson's disease.

Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including alteration in emotional processing and recognition of emotions. We explored the effects of PD on the emotional behavioral ratings using a battery of affective visual stimuli selected from the International Affective Picture System (IAPS).

Methods: Twenty-two patients diagnosed with idiopathic PD and 22 healthy controls (HC), matched by age, gender, and education, were enrolled in the study.