Movement Disorders Clinical Practice最新文献

Background: Wilson's disease (WD) results from pathogenic ATP7B gene variations, causing copper accumulation mainly in the liver, brain, and kidneys.

Objectives: In India, despite studies on ATP7B variants, WD often goes undiagnosed, with the prevalence, carrier rate, and mutation spectrum remaining unknown.

Methods: A multicenter study examined genetic variations in WD among individuals of Indian origin via whole exome sequencing. The study used the InDelible structural variants calling pipeline and conducted molecular dynamic simulations on variants of uncertain significance (VUS) in ATP7B AlphaFold protein structures. Additionally, a high-throughput gene screening panel for WD was developed.

Results: This study examined 128 clinically diagnosed cases of WD, revealing 74 genetically confirmed cases, 22 with ATP7B variants, and 32 without. Twenty-two novel ATP7B gene variants were identified, including a 322 bp deletion classified as a structural variant. Molecular dynamics simulations highlighted the potential deleterious effects of 11 ATP7B VUS. Gene burden analysis suggested associations with ANO8, LGR4, and CDC7. ATP7B gene hotspots for pathogenic variants were identified. Prevalence and carrier rates were determined as one in 18,678 and one in 67, respectively. A multiplex sequencing panel showed promise for accurate WD diagnosis.

Conclusions: This study offers crucial insights into WD's genetic variations and prevalence in India, addressing its underdiagnosis. It highlights the novel genetic variants in the ATP7B gene, the involvement of other genes, a scalable, cost-effective multiplex sequencing panel for WD diagnosis and management and promising advancements in WD care.

Background: Psychosis and cognitive decline often co-occur in Parkinson's Disease (PD), which complicates assessment.

Objective: We measured agreement between patients with PD and dementia (PDD) and care partners (CPs) in their independent evaluation of PD-related psychotic symptoms.

Methods: We compared responses to a PD psychosis rating scale (SAPS-PD) in 21 dyads of patients with PDD and cognitively normal CPs. We assessed the concordance of responses using the intraclass correlation coefficient (ICC). Following the psychosis assessment, the clinician used all available information and adjudicated who provided the most reliable responses.

Results: Dyads demonstrated poor concordance in summary scores (ICC = 0.464). Six of the nine individual items had poor agreement. The clinician adjudicated the patient's response as the more reliable in 71.4% of cases.

Conclusions: Although many psychotic symptoms are internal and not observable, in the context of PDD, both patient and CP inputs are valuable, but final adjudication favors patient responses.

Background: Persons with Parkinson's disease (PD) experience progressive motor and non-motor symptoms which may influence their ability to drive a car. This is experienced as a massive challenge by many affected individuals, for whom being able to drive a car is vital to maintain functional independence.

Objectives: We assessed how the diagnosis of PD affected the possession of a driving license, how people with PD had adapted their driving style, and to what extent they had communicated about their driving ability with their healthcare professionals. We also evaluated their knowledge on insurance- and Driver and Vehicle Licensing Agency (DVLA)-related implications.

Method: A cross-sectional 10-item survey was completed by 540 participants of a population-based cohort of persons with PD in the Netherlands (PRIME-NL study).

Results: Participants had a mean age of 70 years and disease duration of 7.3 years. 84% possessed a valid driving license. Of those who gave up their license, this was done mostly (78%) on a voluntarily basis. Forty percent of those with a driving license adjusted their driving style. Over 50% of respondents had not discussed the impact of PD on their driving ability with their healthcare professionals. Although not compulsory by Dutch law, 52% of the respondents had informed the DVLA about their diagnosis.

Conclusion: This study highlights the need for information and support from healthcare professionals to proactively address driving in their clinical practice. This will help persons with PD in their efforts to maintain their driving license for as long as possible.

Background: Preferences for risk disclosure in population-based studies assessing Parkinson's disease (PD) risk have not been assessed so far.

Objectives: To examine preferences for risk disclosure in a subset of the European Healthy Brain Aging (HeBA) multicenter study.

Methods: After a remote PD risk assessment, a structured pilot-questionnaire on risk disclosure was first presented to participants (≥50 years, without neurodegenerative diseases) during in-person visits at the Innsbruck study site.

Results: From the included 81 participants (63% females, median age 65 years), 79% expressed an unconditional desire to be informed about their PD risk. Confronted with a hypothetical scenario of a positive, specific PD test, most would try to live a healthier lifestyle. Regarding future placebo-controlled disease-modification trials, 66% stated they would probably or definitely participate.

Conclusions: This pilot-study shows an open-minded view of participants towards disclosure of risk for future PD and a proactive attitude regarding dealing with one's risk.