Journal of Movement Disorders最新文献

Objective: Mobility limitations and falls are common in people with Parkinson's disease (PwP). A tailored, multidomain intervention has the potential to be more effective in improving mobility safety and preventing falls than exercise alone. This study aimed to explore the feasibility and potential effectiveness of a multidomain fall prevention intervention (Integrate) designed for PwP who fall frequently.

Methods: The home-based intervention was delivered over 6 months by occupational therapists and physiotherapists. The personalized intervention incorporated home fall-hazard reduction, exercise and safer mobility behavior training. Participants received 8 to 12 home visits, and where required, were supported by care-partners to undertake the intervention.

Results: Twenty-nine people (49% recruitment rate, 10% drop-out rate) with moderate to advanced Parkinson's disease, a history of recurrent falls and mild to moderate cognitive impairment participated, with 26 completing the study. Adherence was moderate to high and there were no adverse events related to the intervention. Twenty-one (81%) participants met or exceeded their safer mobility goal on the Goal Attainment Scale. Participants had a median 1.0 point clinically meaningful improvement on the Short Physical Performance Battery. An exploratory analysis indicated fall rates reduced by almost 50% in the six-month follow-up period (IRR 0.51, 95% CI 0.28 - 0.92).

Conclusions: A multidomain occupational therapy and physiotherapy intervention for PwP with recurrent falls was feasible and appeared to improve mobility safety. A randomized trial powered to detect effects on falls and mobility is warranted.

Objective: We aimed to investigate the association between the triglyceride-glucose index, which measures insulin resistance, and the incidence risk of Parkinson's disease.

Methods: Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002-2019). We included 310,021 participants who had no previous history of Parkinson's disease and for which more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson's disease was determined using the code of the International Classification of Diseases 10th edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs.

Results: During a median of 9.64 years (interquartile range 8.72-10.53), 4,587 individuals (1.48%) had Parkinson's disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index scores was associated with a significantly increased risk of Parkinson's disease (Hazard ratio (HR): 1.062, 95% confidence interval (CI): 1.007-1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence risk of Parkinson's disease in a non-diabetes mellitus cohort (HR: 1.093. 95% CI: 1.025-1.165), but not in a diabetes mellitus cohort (HR: 0.990, 95% CI: 0.902-1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson's disease showed a non-linear increasing (J-shape) trend.

Conclusion: Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence risk of Parkinson's disease in the general population, particularly in a non-diabetes mellitus cohort.

Background: Colony stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare, adult onset leukoencephalopathy. Descriptions from the Indian subcontinent remain limited.

Objective: To report four patients with genetically confirmed CSF1R-L from four Asian Indian families, describing clinical, molecular and radiological features.

Methods: All patients underwent clinical examination, MRI brain, and whole exome sequencing to identify causative variants in CSF1R gene. We also reviewed published Indian cases with CSF1R-L.

Results: Age at enrolment ranged from 34-40 years. Duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioural syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis in one patient. We identified four different variants (three missense, one inframe deletion). Radiological findings demonstrated white matter involvement, and diffusion restriction involving subcortical white matter and pyramidal tracts.

Conclusions: We expand the literature from India with four new cases of CSF1R-L.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and non-dopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer a promising approach to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.