Objective Freezing of gait (FOG) significantly affects quality of life and increases the risk of falls in patients with Parkinson’s disease (PD). Although deep brain stimulation (DBS) of the globus pallidus interna (GPi) is effective in managing motor complications, its efficacy in treating FOG remains inconsistent. This study aimed to determine whether preoperative structural brain connectivity can predict both the presence of FOG and its postoperative improvement following GPi DBS.
Methods We retrospectively analyzed 58 patients with PD who underwent GPi DBS. Preoperative diffusion tensor imaging was used to assess structural connectivity between the volume of activated tissue (VAT) and 82 cortical regions. Machine learning models were developed to predict baseline FOG and postoperative FOG improvement (defined as a ≥1- or ≥2-point reduction) using demographic and connectivity features.
Results Machine learning models incorporating structural connectivity features between the VAT and cortical regions—including the prefrontal, cingulate, and premotor cortices—outperformed models based solely on demographic variables in predicting both the presence of preoperative FOG and postoperative improvement. For example, the support vector machine model to predict FOG improvement (≥1-point improvement) achieved an accuracy of 0.65 with demographic data alone, which increased to 0.77 with the addition of structural connectivity features. Similar performance enhancements were observed in sensitivity analyses using stricter FOG thresholds (≥2-point improvement).
Conclusion Preoperative structural connectivity between the GPi and key cortical regions involved in cognitive control and motor planning predicts FOG responsiveness to DBS. These results highlight the utility of connectomic biomarkers for personalizing DBS strategies and optimizing therapeutic outcomes in patients with advanced PD.
Huntington’s disease (HD) is a neurodegenerative disorder characterized by motor, behavioral, and cognitive impairments and significant impacts on patient quality of life. This evidence-based review, conducted by the Korean Huntington Disease Society task force, systematically examines current pharmacological and nonpharmacological interventions for symptomatic management of HD. Following PRISMA guidelines, databases were searched for studies up to August 2022 that focused on 23 symptoms across four domains: motor, neuropsychological, cognition, and others. This review provides a comprehensive and systematic approach to the management of HD, highlighting the need for more high-quality clinical trials to develop robust evidence-based guidelines.
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Objective Associations between various metabolic conditions and Parkinson’s disease (PD) have been previously identified in epidemiological studies. We aimed to investigate the causal effect of lipid levels, type 2 diabetes mellitus (T2DM), and body mass index (BMI) on PD in a Korean population via Mendelian randomization (MR).
Methods Two-sample MR analyses were performed with inverse-variance weighted (IVW), weighted median, and MR-Egger regression approaches. We identified genetic variants associated with lipid concentrations, T2DM, and BMI in publicly available summary statistics, which were either collected from genome-wide association studies (GWASs) or from meta-analyses of GWAS that targeted only Korean individuals or East Asian individuals, including Korean individuals. The outcome dataset was a GWAS on PD performed in a Korean population.
Results From previous GWASs and meta-analyses, we selected single nucleotide polymorphisms as the instrumental variables. Variants associated with serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, as well as with T2DM and BMI, were selected (n = 11, 19, 17, 89, and 9, respectively). There were no statistically significant causal associations observed between the five exposures and PD using either the IVW, weighted median, or MR-Egger methods (p-values of the IVW method: 0.332, 0.610, 0.634, 0.275, and 0.860, respectively).
Conclusion This study does not support a clinically relevant causal effect of lipid levels, T2DM, and BMI on PD risk in a Korean population.
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Objective Depression in Parkinson’s disease (PD) affects the quality of life of patients. Postural instability and gait disturbance are associated with the severity and prognosis of PD. We investigated the association of depression with axial involvement in early-stage PD patients.
Methods This study involved 95 PD patients unexposed to antiparkinsonian drugs. After a baseline assessment for depression, the subjects were divided into a depressed PD group and a nondepressed PD group. Analyses were conducted to identify an association of depression at baseline with the following outcome variables: the progression to Hoehn and Yahr scale (H-Y) stage 3, the occurrence of freezing of gait (FOG), levodopa-induced dyskinesia, and wearing-off. The follow-up period was 53.40 ± 16.79 months from baseline.
Results Kaplan–Meier survival curves for H-Y stage 3 and FOG showed more prominent progression to H-Y stage 3 and occurrences of FOG in the depressed PD group than in the nondepressed PD group (log-rank p = 0.025 and 0.003, respectively). Depression in drug-naïve, early-stage PD patients showed a significant association with the progression to H-Y stage 3 (hazard ratio = 2.55; 95% confidence interval = 1.32–4.93; p = 0.005), as analyzed by Cox regression analyses. In contrast, the occurrence of levodopa-induced dyskinesia and wearing-off did not differ between the two groups (log-rank p = 0.903 and 0.351, respectively).
Conclusion Depression in drug-naïve, early-stage PD patients is associated with an earlier occurrence of postural instability. This suggests shared nondopaminergic pathogenic mechanisms and potentially enables the prediction of early development of postural instability.
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Methods Participants included 128 PD patients with motor fluctuations. All patients were assessed for motor, nonmotor, and sleep-specific symptoms using the United Parkinson’s Disease Rating Scale (UPDRS), the Korean version of the Nonmotor Symptom Scale, the Parkinson’s Disease Sleep Scale (PDSS), the Epworth Sleepiness Scale, and the Rapid Eye Movement Sleep Behavior Disorder Screening Questionnaire (RBDSQ). We compared the baseline characteristics of patients with sleep disturbance (PDSS score < 120) and those without sleep disturbance (PDSS score ≥ 120). Thirty-nine patients with sleep disturbance who agreed to take LCE at bedtime completed 3-month follow-ups. We analyzed changes in the scores of motor, nonmotor, and sleep symptom scales over the 3 months.
Results PD patients with sleep disturbance were at more advanced disease stages and had more severe motor, nonmotor, and sleep symptoms than those without sleep disturbance. Patients who took LCE at night showed improvements in motor (UPDRS part III, p = 0.007) and sleep symptoms (total PDSS, p < 0.001). Sleep features that benefitted from LCE included not only nocturnal motor components but also insomnia (PDSS items 2 and 3, p = 0.005 and p < 0.001) and rapid eye movement behavior disorder (PDSS item 6, p = 0.002; and RBDSQ, p < 0.001).
Conclusion The use of LCE at bedtime may be a useful treatment for sleep disturbance in advanced PD patients with motor fluctuations.
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