Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease.

Despite substantial progress, causal variants are identified only for a minority of familial Parkinson's disease (PD) cases, leaving high-risk pathogenic variants unidentified. To identify such variants, we uniformly processed exome sequencing data of 2,184 index familial PD cases and 69,775 controls. Exome-wide analyses converged on RAB32 as a novel PD gene identifying c.

Metformin use is associated with reduced mortality risk in diabetic patients with Parkinson's disease.

Introduction: Parkinson's disease (PD) and type-2 diabetes (T2D) arguably share pathophysiologic mechanisms, resulting in a more severe phenotype and progression and diabetes is currently considered a risk factor of PD. Besides, research suggests antidiabetic therapies as potential disease-modifying strategies. The main aim was to assess the impact of a metformin-inclusive antidiabetic treatment on patient all-cause mortality.

The Optimal Targeting for Focused Ultrasound Thalamotomy Differs between Dystonic and Essential Tremor: A 12-Month Prospective Pilot Study.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is increasingly used to treat drug-resistant essential tremor (ET). Data on MRgFUS thalamotomy in dystonic tremor (DT) are anecdotal.

Objectives: To investigate efficacy, safety, and differences in target coordinates of MRgFUS thalamotomy in DT versus ET.

Levodopa Equivalent Dose of Safinamide: A Multicenter, Longitudinal, Case-Control Study.

Background: Effects of dopaminergic medications used to treat Parkinson's disease (PD) may be compared with each other by using conversion factors, calculated as Levodopa equivalent dose (LED). However, current LED proposals on MAO-B inhibitors (iMAO-B) safinamide and rasagiline are still based on empirical approaches.

Objectives: To estimate LED of safinamide 50 and 100 mg.

Disease mechanisms as subtypes: Microbiome.

Abnormalities in gut microbiota have been suggested to be involved in the pathophysiology and progression of Parkinson's disease (PD). Gastrointestinal nonmotor symptoms often precede the onset of motor features in PD, suggesting a role for gut dysbiosis in neuroinflammation and α-synuclein (α-syn) aggregation. In the first part of this chapter, we analyze critical features of healthy gut microbiota and factors (environmental and genetic) that modify its composition.

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study.

Background: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is a safe and effective procedure for drug-resistant tremor in Parkinson's disease (PD).

Objective: The aim of this study was to demonstrate that MRgFUS ventralis intermedius thalamotomy in early-stage tremor-dominant PD may prevent an increase in dopaminergic medication 6 months after treatment compared with matched PD control subjects on standard medical therapy.

Methods: We prospectively enrolled patients with early-stage PD who underwent MRgFUS ventralis intermedius thalamotomy (PD-FUS) and patients treated with oral dopaminergic therapy (PD-ODT) with a 1:2 ratio.

Role of Lysosomal Gene Variants in Modulating GBA-Associated Parkinson's Disease Risk.

Background: To date, variants in the GBA gene represent the most frequent large-effect genetic factor associated with Parkinson's disease (PD). However, the reason why individuals with the same GBA variant may or may not develop neurodegeneration and PD is still unclear.

Objectives: Therefore, we evaluated the contribution of rare variants in genes responsible for lysosomal storage disorders (LSDs) to GBA-PD risk, comparing the burden of deleterious variants in LSD genes in PD patients versus asymptomatic subjects, all carriers of deleterious variants in GBA.

Resting State Functional Connectivity Signatures of MRgFUS Vim Thalamotomy in Parkinson's Disease: A Preliminary Study.

Magnetic Resonance-guided high-intensity Focused Ultrasound (MRgFUS) of the thalamic ventral intermediate nucleus (Vim) for tremor has increasingly gained interest as a new non-invasive alternative to standard neurosurgery. Resting state functional connectivity (rs-FC) correlates of MRgFUS have not been extensively investigated yet. A region of interest (ROI)-to-ROI rs-FC MRI "connectomic" analysis focusing on brain regions relevant for tremor was conducted on 15 tremor-dominant patients with Parkinson's disease who underwent MRgFUS.

Efficacy of safinamide as add-on therapy after subthalamic nucleus deep brain stimulation in Parkinson disease.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective surgical treatment for advanced Parkinson's disease (PD). However, some patients still experience motor fluctuations or dyskinesia after STN-DBS. Safinamide is approved as add-on treatment to levodopa in fluctuating PD patients.

Levodopa-carbidopa intrajejunal infusion in Parkinson's disease: untangling the role of age.

Objectives: Levodopa-Carbidopa Intrajejunal gel (LCIG) infusion is an effective intervention for people with advanced Parkinson's disease (PD). Although age may not be a limiting factor for LCIG implant, no data are available on late elderly PD (LE-PD) subjects. In this cross-sectional, we aimed to demonstrate if older age may impact on quality of life (QoL), motor and non-motor symptoms severity, and profile of side effects in PD treated with LCIG.

Does Gut Microbiota Influence the Course of Parkinson's Disease? A 3-Year Prospective Exploratory Study in de novo Patients.

Background: Although abnormalities in gut microbiota are hypothesized to influence the pathogenesis and clinical phenotype of Parkinson's disease (PD), prospective studies on de novo patients are lacking.

Objective: To preliminarily investigate whether gut microbiota in early untreated PD may predict motor and non-motor features progression over a 3-year period.

Methods: 16S ribosomal RNA gene amplicons were sequenced on fecal samples of 39 de novo PD patients.

The SPID-GBA study: Sex distribution, Penetrance, Incidence, and Dementia in GBA-PD.

Objective: To provide a variant-specific estimate of incidence, penetrance, sex distribution, and association with dementia of the 4 most common Parkinson disease (PD)-associated variants, we analyzed a large cohort of 4,923 Italian unrelated patients with primary degenerative parkinsonism (including 3,832 PD) enrolled in a single tertiary care center and 7,757 ethnically matched controls.

Methods: The p.E326K, p.

Skin Biopsy May Help to Distinguish Multiple System Atrophy-Parkinsonism from Parkinson's Disease With Orthostatic Hypotension.

Background: The differential diagnosis between multiple system atrophy parkinsonism type (MSA-P) and Parkinson's disease with orthostatic hypotension (PD+OH) is difficult because the 2 diseases have a similar clinical picture. The aim of this study is to distinguish MSA-P from PD+OH by immunostaining for abnormal phosphorylated α-synuclein at serine 129 (p-syn) in cutaneous nerves.

Method: We recruited 50 patients with parkinsonism and chronic orthostatic hypotension: 25 patients fulfilled the diagnostic criteria for MSA-P and 25 patients for PD+OH.

Benign versus malignant Parkinson disease: the unexpected silver lining of motor complications.

Objective: We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson's disease (PD).

Methods: Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset.

Effects of COVID-19 on Parkinson's Disease Clinical Features: A Community-Based Case-Control Study.

The impact of coronavirus disease 2019 (COVID-19) on clinical features of Parkinson's disease (PD) has been poorly characterized so far. Of 141 PD patients resident in Lombardy, we found 12 COVID-19 cases (8.5%), whose mean age and disease duration (65.

The gut microbiome in Parkinson's disease: A culprit or a bystander?

In recent years, large-scale metagenomics projects such as the Human Microbiome Project placed the gut microbiota under the spotlight of research on its role in health and in the pathogenesis several diseases, as it can be a target for novel therapeutical approaches. The emerging concept of a microbiota modulation of the gut-brain axis in the pathogenesis of neurodegenerative disorders has been explored in several studies in animal models, as well as in human subjects. Particularly, research on changes in the composition of gut microbiota as a potential trigger for alpha-synuclein (α-syn) pathology in Parkinson's disease (PD) has gained increasing interest.