There are currently no standard diagnostic criteria for characterizing advanced Parkinson’s disease (APD) in clinical practice, a critical component in determining ongoing clinical care and therapeutic strategies, including transitioning to device-aided treatment. The goal of this analysis was to determine the proportion of APD vs. non-advanced PD (non-APD) patients attending specialist PD clinics and to demonstrate the clinical burden of APD. OBSERVE-PD, a cross-sectional, international, observational study, was conducted with 2615 PD patients at 128 movement disorder centers in 18 countries. Motor and non-motor symptoms, activities of daily living, and quality-of-life end points were assessed. The correlation between physician’s global assessment of advanced PD and the advanced PD criteria from a consensus of an international group of experts (Delphi criteria for APD) were evaluated. According to physician’s judgment, 51% of patients were considered to have APD. There was a moderate correlation between physician’s judgment and Delphi criteria for APD (K = 0.430; 95% CI 0.406–0.473). Activities of daily living, motor symptom severity, dyskinesia duration/disability, “Off” time duration, non-motor symptoms, and quality-of-life scores were worse among APD vs. non-APD patients (p < 0.0001 for all). APD patients (assessed by physicians) had higher disease burden by motor and non-motor symptoms compared with non-APD patients and a negative impact on activities of daily living and quality of life. These findings aid in identifying standard APD classification parameters for use in practicing physicians. Improvements in identification of APD patients may be particularly relevant for optimizing treatment strategies including transitioning to device-aided treatment.

Decreased axial rotation, impaired coordination between axial segments and axial tone contribute to gait, balance and postural disorders in Parkinson’s Disease.The aim of our study was to examine t...

The aim of this study was to examine whether cervical stabilization exercises (CSEs) change the effects of conventional exercises (CEs) in patients with PD. Twenty-five patients with PD were randomized into two groups. While the experimental group (EG) received CSEs in addition to CEs, the control group (CG) received only CEs. Both programs lasted 8 weeks. Eighteen participants were able to complete the study. The outcomes were the changes in posture, cervical joint position sense (JPS), balance assessment, 10-m walking tests (10MWT), and the Timed Up & Go (TUG) test. At the end of the study, significant improvement was observed in both groups in terms of trunk rotation angle and pelvic asymmetry, the time parameter of TUG, and the 10MWT (p < 0.05). In the EG, greater improvement was detected in the Berg Balance Scale, static posturography, postural alignment, JPS, and the cadence parameter of TUG (p < 0.05). CEs and CSEs could improve walking speed and posture in patients with PD, but if CSEs are added to CEs, greater improvements could be achieved in JPS and postural control.(Clinical Trials ID: NCT03854747).

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson’s disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a novel gene implicated in parkinsonism and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD to perinatal lethality with neurological manifestations across 17 pedigrees with 24 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy, and may affect proteasomal abundance and assembly in patient-derived fibroblasts. Furthermore, Drosophila and mouse models of PSMF1 loss of function exhibit age-dependent motor impairment, as well as brain-wide mitochondrial membrane depolarization and dopaminergic neurodegeneration in aged flies, and diffuse gliosis in mice. Collectively, our findings unequivocally link defective PSMF1 to early-onset parkinsonism and neurodegeneration, and suggest proteasomal and mitochondrial dysfunction as mechanistic contributors.

The aim of the study was to evaluate the effects of freezing of gait (FOG) on static and dynamic balance.Twenty patients with Parkinson’s disease with and without FOG [PD+FOG (68,6±6,39 years) and ...