Are rare heterozygous SYNJ1 variants associated with Parkinson's disease?

Previous studies have established that rare biallelic SYNJ1 mutations cause autosomal recessive parkinsonism and Parkinson's disease (PD). We analyzed 8165 PD cases, 818 early-onset-PD (EOPD, < 50 years) and 70,363 controls. Burden meta-analysis revealed an association between rare nonsynonymous variants and variants with high Combined Annotation-Dependent Depletion score (> 20) in the Sac1 SYNJ1 domain and PD (Pfdr = 0.

A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking.

Satisfaction with videoconferencing support for levodopa-carbidopa intestinal gel: An observational study.

Background: Levodopa-carbidopa intestinal gel (LCIG) is a continuously delivered Parkinson's disease therapy intended to stabilize plasma levodopa levels. Patients receiving LCIG require education and follow-up. Some LCIG support programs use video-assisted telenursing.

Levodopa-carbidopa intestinal gel for advanced Parkinson's disease: Impact of LRRK2 and GBA1 mutations.

Background: Advanced Parkinson's disease (PD) can be treated with Levodopa-Carbidopa Intestinal Gel (LCIG).

Objective: To compare descriptive data of LCIG treatment in GBA1-PD and LRRK2-PD.

Methods: This multicenter retrospective study compared clinical data obtained from electronic medical records of PD patients treated with LCIG.

-Associated Parkinson's Disease Is a Distinct Entity.

-associated Parkinson's disease (-PD) is increasingly recognized as a distinct entity within the spectrum of parkinsonian disorders. This review explores the unique pathophysiological features, clinical progression, and genetic underpinnings that differentiate -PD from idiopathic Parkinson's disease (iPD). -PD typically presents with earlier onset and more rapid progression, with a poor response to standard PD medications.

The yield of genetic workup for middle-aged and elderly patients with neurological disorders in a real-world setting.

Genetic workup is becoming increasingly common in the clinical assessment of neurological disorders. We evaluated its yield among middle-aged and elderly neurological patients, in a real-world context. This retrospective study included 368 consecutive Israeli patients aged 50 years and older (202 [54.

Quantifying Changes in Dexterity as a Result of Piano Training in People with Parkinson's Disease.

People with Parkinson's disease often show deficits in dexterity, which, in turn, can lead to limitations in performing activities of daily life. Previous studies have suggested that training in playing the piano may improve or prevent a decline in dexterity in this population. In this pilot study, we tested three participants on a six-week, custom, piano-based training protocol, and quantified dexterity before and after the intervention using a sensor-enabled version of the nine-hole peg test, the box and block test, a test of finger synergies using unidimensional force sensors, and the Quantitative Digitography test using a digital piano, as well as selected relevant items from the motor parts of the MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Parkinson's Disease Questionnaire (PDQ-39) quality of life questionnaire.

Are rare heterozygous variants associated with Parkinson's disease?

Previous studies have suggested that rare biallelic mutations may cause autosomal recessive parkinsonism and Parkinson's disease (PD). Our study explored the impact of rare variants in non-familial settings, including 8,165 PD cases, 818 early-onset PD (EOPD, <50 years) and 70,363 controls. Burden meta-analysis using optimized sequence Kernel association test (SKAT-O) revealed an association between rare nonsynonymous variants in the Sac1 SYNJ1 domain and PD (P=0.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Background: Variants in the gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis.

Safety and efficacy of continuous subcutaneous levodopa-carbidopa infusion (ND0612) for Parkinson's disease with motor fluctuations (BouNDless): a phase 3, randomised, double-blind, double-dummy, multicentre trial.

Background: Conventional oral levodopa therapy for the treatment of Parkinson's disease can be associated with variations in plasma concentrations. Levodopa infusion strategies might provide more consistent drug delivery and fewer motor fluctuations. We aimed to assess the safety and efficacy of a continuous 24 h/day subcutaneous infusion of ND0612 (a levodopa-carbidopa solution) compared with oral immediate-release levodopa-carbidopa for the treatment of motor fluctuations in people with Parkinson's disease.

Chenodeoxycholic acid (CDCA) treatment during pregnancy in women with cerebrotendinous xanthomatosis (CTX): Lessons learned from 19 pregnancies.

Purpose: Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder. Biallelic pathogenic variants in CYP27A1, encoding for sterol 27-hydroxylase, impair cholic acid (CA) and chenodeoxycholic acid (CDCA) synthesis and lead to accumulation of cholestanol and C bile alcohols. Treatment with CDCA decreases the accumulation of these harmful metabolites and slows disease progression.

Are LRRK2 p.G2019S or GBA1 variants associated with long-term outcomes of deep brain stimulation for Parkinson's disease?

Background: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized.

Home-based monitoring of persons with advanced Parkinson's disease using smartwatch-smartphone technology.

Movement deterioration is the hallmark of Parkinson's disease (PD), characterized by levodopa-induced motor-fluctuations (i.e., symptoms' variability related to the medication cycle) in advanced stages.

The Parkinson's disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons.

Variants in the gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson's disease (PD). However, neither the specific variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis.

Adult-onset Alexander disease among patients of Jewish Syrian descent.

Alexander disease (AxD) is a rare autosomal dominant leukodystrophy caused by heterozygous mutations in the glial fibrillary acid protein (GFAP) gene. The age of symptoms onset ranges from infancy to adulthood, with variable clinical and radiological manifestations. Adult-onset AxD manifests as a chronic and progressive condition, characterized by bulbar, motor, cerebellar, and other clinical signs and symptoms.

Differential gait adaptation patterns in Parkinson's disease - a split belt treadmill pilot study.

Background: Interventions using split belt treadmills (SBTM) aim to improve gait symmetry (GA) in Parkinson's disease (PD). Comparative effects in conjugated SBTM conditions were not studied systematically despite potentially affecting intervention outcomes. We compared gait adaptation effects instigated by SBTM walking with respect to the type (increased\decreased speed) and the side (more/less affected) of the manipulated belt in PD.

Association of Rare Variants in ARSA with Parkinson's Disease.

Background: Several lysosomal genes are associated with Parkinson's disease (PD), yet the association between PD and ARSA remains unclear.

Objectives: To study rare ARSA variants in PD.

Methods: To study rare ARSA variants (minor allele frequency < 0.

Heart-rate variability as a new marker for freezing predisposition in Parkinson's disease.

Introduction: Freezing of gait (FoG) is a debilitating symptom of advanced Parkinson's disease (PD) characterized by a sudden, episodic stepping arrest despite the intention to continue walking. The etiology of FoG is still unknown, but accumulating evidence unraveled physiological signatures of the autonomic nervous system (ANS) around FoG episodes. Here we aim to investigate for the first time whether detecting a predisposition for upcoming FoG events from ANS activity measured at rest is possible.

Long-term safety of medical cannabis in Parkinson's disease: A retrospective case-control study.

Background: Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson's disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or its safety profile. This study examined the effects of MC on PD in a real-life setting.

Bilateral leg stepping coherence as a predictor of freezing of gait in patients with Parkinson's Disease walking with wearable sensors.

Unlabelled: Freezing of Gait (FOG) is among the most debilitating symptoms of Parkinson's Disease (PD), characterized by a sudden inability to generate effective stepping. In preparation for the development of a real-time FOG prediction and intervention device, this work presents a novel FOG prediction algorithm based on detection of altered interlimb coordination of the legs, as measured using two inertial movement sensors and analyzed using a wavelet coherence algorithm.

Methods: Fourteen participants with PD (in OFF state) were asked to walk in challenging conditions (e.