Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Factor analysis and clustering of motor and psychiatric dimensions in idiopathic blepharospasm.

Introduction: Idiopathic blepharospasm is a clinically heterogeneous form of focal dystonia, also associated with psychiatric symptoms. The identification of the most relevant sets of motor and psychiatric manifestations may help better understand the specific phenomenology of the condition and delineate blepharospasm subtypes more accurately.

Methods: Patients with idiopathic blepharospasm were from the Dystonia Coalition project.

Association of Early fMRI Connectivity Alterations With Different Cognitive Phenotypes in Patients With Newly Diagnosed Parkinson Disease.

Background And Objectives: According to the dual syndrome hypothesis, patients with Parkinson disease (PD) with visuospatial deficits are more likely to progress to dementia, compared with patients with a prevalent dysexecutive syndrome. In this study, we aimed to investigate whether early connectivity changes in the dorsolateral prefrontal cortex (DLPFC) and the precuneus (PCun)-which are critical to fronto-executive and visuospatial functions, respectively-can identify distinct cognitive phenotypes in cognitively intact newly diagnosed patients with PD.

Methods: Newly diagnosed, drug-naïve patients with PD (≤2 years from clinical onset) with normal Montreal Cognitive Assessment (MoCA), were consecutively enrolled from our Movement Disorders Clinics in Italy.

Neurophysiological Features of Tremor during Walking in Parkinson's Disease.

Background: In Parkinson's Disease (PD), upper limb tremor during walking (TW) is observed and clinical observations suggest it may represent a variant of rest tremor. However, its neurophysiological characteristics remain unexplored.

Objectives: This study compared the neurophysiological features of TW with other PD tremors and tested whether TW arises from reduced ipsilateral arm swing.

Improvement of fatigue, depression, and processing speed two weeks post Natalizumab infusion in Multiple Sclerosis: No difference between standard and extended interval dosing schedules.

Background: Fatigue, depression and slow processing speed are debilitating symptoms in people with Relapsing-Remitting Multiple Sclerosis (RRMS) that significantly impacts on the quality of life. Natalizumab, a disease-modifying treatment, improves clinical symptoms but questions remain about the comparative efficacy between its standard interval dosing (SID) and extended interval dosing (EID) schedules.

Objective: To examine the impact of short term natalizumab dosing schedules-SID versus EID-on the so called "invisible symptoms", specifically focusing on symptom exacerbation during the 'wearing-off' phase before infusion and the subsequent relief post-infusion.

Amelioration of Focal Hand Dystonia via Low-Frequency Repetitive Somatosensory Stimulation.

Background: Dystonia presents a growing concern based on evolving prevalence insights. Previous research found that, in cervical dystonia, high-frequency repetitive somatosensory stimulation (RSS; HF-RSS) applied on digital nerves paradoxically diminishes sensorimotor inhibitory mechanisms, whereas low-frequency RSS (LF-RSS) increases them. However, direct testing on affected body parts was not conducted.

Neurophysiological markers of motor compensatory mechanisms in early Parkinson's disease.

Compensatory mechanisms in Parkinson's disease are defined as the changes that the brain uses to adapt to neurodegeneration and progressive dopamine reduction. Motor compensation in early Parkinson's disease could, in part, be responsible for a unilateral onset of clinical motor signs despite the presence of bilateral nigrostriatal degeneration. Although several mechanisms have been proposed for compensatory adaptations in Parkinson's disease, the underlying pathophysiology is unclear.

Insight into motor fatigue mechanisms in natalizumab treated multiple sclerosis patients with wearing off.

Motor fatigue in Multiple Sclerosis (MS) is due to reduced motor cortex (M1) output and altered sensorimotor network (SMN) modulation. Natalizumab, a disease-modifying therapy, reduces neuroinflammation and improves fatigue. However, some patients treated with natalizumab experience fatigue recurrence ('wearing-off') before subsequent infusions.

Mapping Motor Cortical Network Excitability and Connectivity Changes in De Novo Parkinson's Disease.

Background: Transcranial magnetic stimulation-electroencephalography (TMS-EEG) has demonstrated decreased excitability in the primary motor cortex (M1) and increased excitability in the pre-supplementary motor area (pre-SMA) in moderate-advanced Parkinson's disease (PD).

Objectives: The aim was to investigate whether these abnormalities are evident from the early stages of the disease, their behavioral correlates, and relationship to cortico-subcortical connections.

Methods: Twenty-eight early, drug-naive (de novo) PD patients and 28 healthy controls (HCs) underwent TMS-EEG to record TMS-evoked potentials (TEPs) from the primary motor cortex (M1) and the pre-SMA, kinematic recording of finger-tapping movements, and a 3T-MRI (magnetic resonance imaging) scan to obtain diffusion tensor imaging (DTI) reconstruction of white matter (WM) tracts connecting M1 to the ventral lateral anterior thalamic nucleus and pre-SMA to the anterior putamen.

Understanding the role of cerebellum in early Parkinson's disease: a structural and functional MRI study.

Increasing evidence suggests that the cerebellum may have a role in the pathophysiology of Parkinson's disease (PD). Hence, the scope of this study was to investigate whether there are structural and functional alterations of the cerebellum and whether they correlate with motor and non-motor symptoms in early PD patients. Seventy-six patients with early PD and thirty-one age and sex-matched healthy subjects (HS) were enrolled and underwent a 3 T magnetic resonance imaging (MRI) protocol.

The Role of Cerebellum and Basal Ganglia Functional Connectivity in Altered Voluntary Movement Execution in Essential Tremor.

Substantial evidence highlights the role of the cerebellum in the pathophysiology of tremor in essential tremor (ET), although its potential involvement in altered movement execution in this condition remains unclear. This study aims to explore potential correlations between the cerebellum and basal ganglia functional connectivity and voluntary movement execution abnormalities in ET, objectively assessed with kinematic techniques. A total of 20 patients diagnosed with ET and 18 healthy subjects were enrolled in this study.

Clinical and kinematic characterization of parkinsonian soft signs in essential tremor.

Background: Subtle parkinsonian signs, i.e., rest tremor and bradykinesia, are considered soft signs for defining essential tremor (ET) plus.

Evaluating the Diagnostic Potential of Combined Salivary and Skin Biomarkers in Parkinson's Disease.

Oligomeric alpha-synuclein (α-syn) in saliva and phosphorylated α-syn deposits in the skin have emerged as promising diagnostic biomarkers for Parkinson's disease (PD). This study aimed to assess and compare the diagnostic value of these biomarkers in discriminating between 38 PD patients and 24 healthy subjects (HSs) using easily accessible biological samples. Additionally, the study sought to determine the diagnostic potential of combining these biomarkers and to explore their correlations with clinical features.

Blood-based biological ageing and red cell distribution width are associated with prevalent Parkinson's disease: findings from a large Italian population cohort.

Background: Aging clocks tag the actual underlying age of an organism and its discrepancy with chronological age and have been reported to predict incident disease risk in the general population. However, the relationship with neurodegenerative risk and in particular with Parkinson's Disease (PD) remains unclear, with few discordant findings reporting associations with both incident and prevalent PD risk.

Objective: To clarify this relationship, we computed a common aging clock based on blood markers and tested the resulting discrepancy with chronological age (ΔPhenoAge) for association with both incident and prevalent PD risk.

A systematic review of salivary biomarkers in Parkinson's disease.

The search for reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis, to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies. Despite the need for non-invasively accessible biomarkers, the majority of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers, which require invasive collection procedures. Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.

Can Repetitive Transcranial Magnetic Stimulation (rTMS) Promote Neurogenesis and Axonogenesis in Subacute Human Ischemic Stroke?

Background: Ischemic stroke may trigger neuroplastic changes via proliferation, migration towards the lesion, and differentiation of neuroprogenitor cells into mature neurons. Repetitive Transcranial Magnetic Stimulation (rTMS) may promote brain plasticity. This study aimed to assess rTMS's effect on post-stroke endogenous neuroplasticity by dosing plasma miRs 17~92, Netrin-1, Sema3A, and BDNF.

Neural control of blinking.

Blinking is a motor act characterized by the sequential closing and opening of the eyelids, which is achieved through the reciprocal activation of the orbicularis oculi and levator palpebrae superioris muscles. This stereotyped movement can be triggered reflexively, occur spontaneously, or voluntarily initiated. During each type of blinking, the neural control of the antagonistic interaction between the orbicularis oculi and levator palpebrae superioris muscles is governed by partially overlapping circuits distributed across cortical, subcortical, and brainstem structures.

Does sex influence the natural history of idiopathic adult-onset dystonia?

Background: Several earlier studies showed a female predominance in idiopathic adult-onset dystonia (IAOD) affecting the craniocervical area and a male preponderance in limb dystonia. However, sex-related differences may result from bias inherent to study design. Moreover, information is lacking on whether sex-related differences exist in expressing other dystonia-associated features and dystonia spread.

Interhemispheric imbalance and bradykinesia features in Parkinson's disease.

In patients with Parkinson's disease, the connectivity between the two primary motor cortices may be altered. However, the correlation between asymmetries of abnormal interhemispheric connections and bradykinesia features has not been investigated. Furthermore, the potential effects of dopaminergic medications on this issue remain largely unclear.

Exploring the Central Mechanisms of Botulinum Toxin in Parkinson's Disease: A Systematic Review from Animal Models to Human Evidence.

Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson's disease (PD).

Theta-tACS modulates cerebellar-related motor functions and cerebellar-cortical connectivity.

Objective: 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.