Objectives: This study investigated whether targeting mood via sequential bilateral dorsolateral prefrontal cortex (DLPFC) tDCS could favorably affect motor function in patients maintaining a stable medication 'ON' state. Additionally, we employed wearable smart devices to objectively evaluate real-world changes in daily activity and sleep patterns, complementing traditional clinician-rated scales.Methods: PD patients with mild-to-moderate depressive symptoms were enrolled. All participants completed a 7-day baseline monitoring period using a smart band. Participants received ten sessions of bilateral tDCS targeting the DLPFC (anode F3, cathode F4) at 2 mA for 30 min, three times a week. Clinical assessments and smart band monitoring were repeated during the final week of treatment. Pre-post changes and correlations were analyzed while controlling for potential confounders.Results: Following tDCS, it was significant improvements in K-MADRS, STAI, AS, UPDRS part III, and PDQ-39. Smart device data showed a significant increase in daily step counts after treatment, while changes in physical activity time and sleep duration were not significant. Changes in step count were strongly correlated with improvements in apathy, and this relationship remained significant after confounding variables (rho = -0.76, p < 0.001).Conclusions: Bilateral DLPFC tDCS significantly improved mood and motor function in patients with PD. Smart band data further showed an increase in daily step counts after the intervention, with reductions in apathy. These findings suggest that tDCS may enhance goal-directed behavior by modulating mood-related pathways, highlighting apathy as an important therapeutic target in PD.

Background:Bilateral motor asymmetry is a hallmark feature of Parkinson's disease (PD). However, few studies have quantitatively examined this feature in patients with scans without evidence of dopaminergic deficit (SWEDD). This study aimed to investigate upper limb asymmetry in bradykinesia among PD and SWEDD patients using gyro sensors, focusing on finger tapping and forearm rotation task. Methods:We recruited 23 early-stage, drug-naïve PD patients, 23 SWEDD patients, and 20 age-matched healthy controls. We recorded gyro sensor signals during 15-s finger tapping and forearm rotation tasks. Bilateral asymmetry indices were calculated and compared among groups. In addition, repeated measure analysis of variance (ANOVA) was used to examine the interaction of task and group, and Spearman correlation analysis was conducted with clinical motor scores. Results:No significant group differences were found during finger tapping. However, during forearm rotation, PD patients exhibited significantly greater asymmetry than SWEDD patients in several indices, including RMS angular velocity, peak angular displacement, peak power, and total power. Task × group interaction effects were significant only in forearm rotation, and asymmetry indices from forearm rotation showed significant correlations with clinical motor scores. Conclusions:Forearm rotation is a sensitive task for detecting motor asymmetry in PD and for differentiating PD from SWEDD. These results suggest that quantitative motor asymmetry indices using wearable sensors could aid clinicians in the identification of potential SWEDD.

Freezing of gait (FOG) is a common and debilitating symptom of Parkinson's disease (PD). Despite its significant clinical impact, the underlying pathophysiological mechanisms of FOG remain poorly understood. Given the clinical heterogeneity of FOG and its occurrence in various disorders, not only dopaminergic dysfunction but also multiple nondopaminergic neurotransmitter systems play a role in this phenomenon. In this review, we offer a comprehensive overview of current evidence regarding the contributions of various neurotransmitters to FOG, including dopamine, acetylcholine, norepinephrine, serotonin, glutamate, and gamma-aminobutyric acid (GABA). While dopaminergic dysfunction is particularly relevant in levodopa-responsive forms of FOG, the occurrence of paradoxical ON-state freezing and levodopa-unresponsive FOG underscores dopamine's limited and nonlinear role in gait control. Degeneration of the cholinergic system has been linked to impaired gait automaticity, attentional control, and postural stability, thereby exacerbating freezing, especially in cognitively triggered and levodopa-unresponsive FOG. Additionally, noradrenergic dysfunction may impair attentional and adaptive control of gait, making locomotor networks more susceptible to freezing under stress or cognitive load. Although evidence is limited, the serotonergic system is also thought to be involved in FOG. An imbalance between glutamatergic excitation and GABAergic inhibition within cortico-basal ganglia-brainstem circuits may destabilize locomotor network dynamics and contribute to freezing, as supported by neuroimaging and pharmacological studies. The ways in which these neurotransmitter systems contribute to FOG are multifactorial and involve complex interactions within distributed locomotor networks.

Classification of fallers in Parkinson's disease (PD) is challenging due to the heterogenous motor and non-motor symptoms. We developed a machine learning model integrating clinical and gait data to identify key clinical markers of faller status in PD. Of 468 participants, 396 with complete data were analyzed, with 298 assigned to training from one center and 98 to external validation from the other. Clinical assessments and GAITRite-derived gait metrics were obtained. Fall history classified participants as PD fallers, PD non-fallers, or healthy controls. Features were selected through statistical and importance-based approaches, and seven machine learning algorithms were trained. The Extra Trees classifier utilizing statistics-based feature selection demonstrated the highest performance (accuracy 88% internal, 89% external). Three principal domains consistently emerged: fear of falling (FoF), balance/gait measures (stride length, velocity, 360° rotation), and autonomic dysfunction. These findings support the feasibility of externally validated, multidomain machine learning-based faller classification in PD.

BACKGROUND AND PURPOSE:Polypharmacy is common in Parkinson's disease (PD). This includes appropriate medications for PD-related symptoms and comorbid conditions, but also potentially inappropriate medications (PIMs). We aimed to determine the prescribing trends of PIMs based on the 2019 Beers Criteria in Korean patients with PD. METHODS:This retrospective observational study analyzed PD patients aged 40 years or older whose PIM prescribing patterns from 2014 to 2019 were included in the HIRA (Korean Health Insurance Review and Assessment Service) nationwide claims database in South Korea. The prevalence and usage were analyzed for both overall PIMs and PIMs that can exacerbate PD symptoms (PIMPDs). Additionally, the most frequently prescribed PIMs and PIMPDs were investigated. RESULTS:PIMs were used at least once in 38.3% of 257,142 patients with PD. The mean number of PIM items used per patient was 2.61. The PIM usage ratio, corresponding to the proportion of the total amount of PIMs to all medications per patient, was 19.7%. The proportion of patients taking PIMs among all PD patients decreased significantly up to 2018 but then increased in 2019, while the PIM usage ratio increased steadily up to 2018 and then decreased in 2019. Excluding the representative PD medications, the most frequently prescribed PIM was amitriptyline. PIMPDs were also commonly used, including levosulpiride and haloperidol. CONCLUSIONS:The prevalence and usage of PIMs were high in Korean PD patients during 2014-2019, and the utilization of PIMPDs persisted throughout this period. These findings can be used to develop evidence-based guidelines for robust polypharmacy management strategies to ensure the safety of medications used by PD patients.

Although extensive research has been conducted on extramedian sensory manifestations observed in carpal tunnel syndrome (CTS) patients, extraterritorial motor dysfunction has received relatively little attention from clinicians. This study aimed to explore extraterritorial motor performance in CTS patients utilizing a gyrosensor. We measured angular velocity signals during rotational movements of the forearm in 37 patients with mild-to-moderate CTS and 42 control subjects. Four quantitative analysis indices were calculated from the gyro sensor data. All patients completed the Boston-Questionnaire, including 11 items from the symptom severity scale (SSS) and 8 items from the functional severity scale (FSS). Motor symptoms (MOTOR) were assessed by calculating mean scores for SSS items 7 (hand weakness) and 11 (hand clumsiness). CTS patients showed significantly lower values in all forearm pronation/supination parameters compared to control subjects (RMS angular velocity and total power of angular velocity, P<0.001; RMS angular displacement, P=0.001; peak power of angular velocity, P=0.022). Moreover, all analysis indices showed significant correlation with FSS scores (r=-0.339 to -0.420). RMS angular velocity, RMS angular displacement, and total power also showed a negative correlation with MOTOR scores (r=-0.262 to -0.373). Our study demonstrated extraterritorial motor impairment in individuals with early-stage CTS, closely associated with functional impairment and motor symptoms, underscoring its potential clinical relevance. Further investigation is warranted to delineate its precise mechanism.

Our study aimed to examine differences in postural sway variables between Parkinson's disease (PD) patients with freezing of gait (FOG) and those without freezing of gait (NFOG), with a particular focus on their fall history. Eighty-one patients with PD participated in this study, including 32 fallers and 49 nonfallers. In the faller group, 21 patients were classified into the FOG group, while 11 patients were categorized into the NFOG group. Each patient underwent a 30 s static postural balance assessment while standing on a custom-developed force plate. The center of pressure (COP) data was filtered and analyzed to derive key COP-based outcome measures. Independent t-tests were conducted to compare the FOG and NFOG groups within both faller and nonfaller subgroups. Spearman's rank correlation analysis was conducted to investigate the association between COP-based outcomes and Tinetti balance scores. In the nonfaller group, FOG patients exhibited significantly greater mean distance (p< 0.05), particularly in the mediolateral direction (p< 0.01), compared to NFOG patients. Anterior-posterior (AP) peak power was also significantly higher in the FOG group (p< 0.05), along with a larger sway area (p< 0.05). However, no significant differences were noted within the faller group (p> 0.05). Notably, in the nonfaller NFOG group, most COP-based variables were significantly correlated with Tinetti balance scores (r=-0.463 - 0.535, p< 0.05), with stronger correlations observed in the mediolateral direction. No significant correlations were found in other groups (p> 0.05). These findings may help clinicians in better distinguish between patients with and without FOG, considering their fall history.

Diminished facial expression, a hallmark symptom of Parkinson's disease (PD), significantly impacts non-verbal communication and social interactions. This study explores the use of temporal facial variability (TVV) as a objective measure for motor impairment severity in de-novo PD patients. A cohort of 42 participants performed structured speech tasks, and their facial dynamics were captured using high-resolution 3D sensors. Advanced geometric and statistical analyses, including radial curve tensors and temporal volume variation metrics, were applied to quantify facial muscle activity. Clustering and regression analyses revealed a significant association between TVV and UPDRS Part III scores, with lower facial variability correlating with greater motor impairment. The findings suggest that temporal volume variability (TVV) may serve as a promising non-invasive marker to assist in the early detection and monitoring of Parkinson's disease. This structured speech task methodology could potentially complement existing clinical tools, contributing to improved diagnostic precision.

Parkinson’s disease (PD) is an incurable condition significantly impacting the quality of life for millions of patients. Much research is devoted to developing early diagnostic tools to ensure symptomatic treatment can start as early as possible. To aid this, here we present a computer vision framework based on automatic gait analysis from a single video camera and evaluate its effectiveness for two challenging datasets containing patients with only “Mild” or “Slight” symptoms. We analyze classification performance using two pose tracking frameworks, six different feature extraction methods, and three classification schemes. In addition, we identify and discuss limitations of a previous approach using Dynamic Time Warping (DTW). Overall, our results show that the gait feature of Margin of Stability allows us to reliably identify PD at 98.8

Background:Limited trials are evaluating the efficacy of monoamine oxidase B inhibitors as an adjunct to levodopa monotherapy for early wearing-off in Parkinson's disease (PD). We evaluated the efficacy and safety of safinamide in patients with fluctuating PD treated with levodopa monotherapy. Methods:This pooled analysis used data from the J-SILVER and KEEP studies and targeted patients with PD experiencing wearing-off who received safinamide as adjunct to levodopa monotherapy. Efficacy endpoints were mean changes in 39-item Parkinson's Disease Questionnaire (PDQ-39), Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts III and IV, and daily OFF time at 18 weeks of treatment. Results:Of 54 patients (J-SILVER, N = 24; KEEP, N = 30), 41 completed the studies. Although not statistically significant, the change in PDQ-39 Summary Index exceeded the minimal clinical important difference (mean [standard deviation (SD)]: -2.2 [7.5], p = 0.094) at Week 18. Significant improvements in MDS-UPDRS Parts III and IV scores and daily OFF time were observed at Week 18 from baseline (mean [SD]: -2.8 [8.5]; p = 0.043, -1.3 [2.7]; p = 0.004, and -1.2 [3.5] hours; p = 0.041, respectively). Adverse events occurred in 24 patients (43.6%) and adverse drug reactions (ADRs) occurred in 12 patients (21.8%). ADRs with an incidence ≥5% were dyskinesia (3 events, 5.5%). In subgroup analyses, improvements in PDQ-39 Summary Index and MDS-UPDRS Parts III and IV were significant in patients aged ≥75 years (p = 0.039, p = 0.029, and p = 0.025, respectively). Conclusion:Safinamide as an adjunct to levodopa monotherapy was effective for early wearing-off without any new tolerability concerns. Safinamide was particularly beneficial in elderly patients.

This study aims to investigate the effects of sequential transcranial direct current stimulation (tDCS) treatments on sleep disturbances and their interplay with mood and motor symptoms in Parkinson’s disease (PD) patients, with smart devices used to objectively monitor sleep patterns and activity levels. Twenty PD patients with depressive symptoms participated in ten sessions of tDCS treatment. Clinical assessments included the Unified Parkinson’s Disease Rating Scale (UPDRS), Montgomery-Åsberg Depression Rating Scale (MADRS), State-Trait Anxiety Inventory (STAI), Apathy Scale (AS), and Parkinson’s Disease Questionnaire-39 items (PDQ-39). Smart devices recorded sleep duration, patterns, and daily activity levels. Pre- and post-tDCS data were analyzed using paired t-tests, Pearson’s correlation, and regression analyses to evaluate changes in sleep, mood, and motor outcomes. Although smart device data indicated no significant changes in total sleep duration post-tDCS, there was a significant increase in step counts (p = 0.012), suggesting an elevation in arousal levels. This increased arousal was correlated with mood improvements, as demonstrated by changes in MADRS scores (r = -0.47, p = 0.04). Regression analysis showed that changes in depressive symptoms explained 21.8% of the variance in step count (R² = 0.218, p = 0.04). However, no direct relationship was found between motor symptom improvements (UPDRS) and sleep duration. While tDCS did not extend total sleep duration, the observed increase in step counts implies heightened arousal levels, potentially driven by improved mood. Smart device monitoring provided objective data on activity and sleep, supporting its use in comprehensive PD management. These findings underscore the importance of evaluating arousal levels and mood as interconnected components influencing sleep and daily activity in PD patients.

Objective and quantitative evaluation of the gait has a very important implications in patients with neurological disorders. Such evaluation is possible by gait analysis system and can be clinically useful. Gait analysis can be performed through laboratory systems, non-wearable sensors, and/or wearable sensors. Using this system, neurologists can measure objective evaluation and treatment effects in patients with movement disorders, including Parkinson's disease, normal pressure hydrocephalus, stroke, Alzheimer's disease, and normal aging. In this review, we aimed to introduce the currently available gait analysis systems, and also present what you need to know in clinical applications.

Background: Several studies have reported atrophy of the vagus nerve (VN) in patients with parkinsonism, but most reports have been conducted on advanced patients group. This study aimed to compare VN size in patients with Parkinson's disease (PD) according to the disease stages and nondegenerative parkinsonian (non-PD) patients using high-resolution ultrasonography (HRUS).

Background: We aimed to evaluate Safinamide as add-on therapy, improving motor symptoms as well as patients' quality of life. This study was specifically designed to investigate the efficacy of safinamide maintained without escalating the dose of levodopa and dopamine agonist during the treatment period.

Objective The Scales for Outcomes in Parkinson’s Disease–Cognition (SCOPA-Cog) was developed to assess cognition in patients with Parkinson’s disease (PD). In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPACog (K-SCOPA-Cog).Methods We enrolled 129 PD patients with movement disorders from 31 clinics in South Korea. The original version of the SCOPA-Cog was translated into Korean using the translation-retranslation method. The test–retest method with an intraclass correlation coefficient (ICC) and Cronbach’s alpha coefficient were used to assess reliability. Spearman’s rank correlation analysis with the Montreal Cognitive Assessment-Korean version (MOCA-K) and the Korean Mini-Mental State Examination (K-MMSE) were used to assess concurrent validity.Results The Cronbach’s alpha coefficient was 0.797, and the ICC was 0.887. Spearman’s rank correlation analysis revealed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively).Conclusion Our results demonstrate that the K-SCOPA-Cog has good reliability and validity.

Background: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. ObjectivesTo evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. Methods: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. Results: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. Conclusions: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.

This multicentre, prospective, single-arm study evaluated safinamide as add-on therapy to levodopa in Korean patients with Parkinson’s disease (PD) with motor fluctuations with ≥ 1.5 h of “off” time daily, who took levodopa ≥ 3 times/day (n = 199). Baseline levodopa and dopamine agonist doses were maintained without escalation during the 18-week treatment period. Participants received safinamide 50 mg/day for 2 weeks and 100 mg/day thereafter. PD diaries and questionnaires (Parkinson’s Disease Questionnaire, PDQ-39; Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, MDS–UPDRS part 3 and part 4; King’s Parkinson’s Disease Pain Scale, KPPS; Mini-Mental State Examination, MMSE) were assessed at baseline and at week 18. Treatment-emergent adverse events (TEAEs) were recorded. Mean disease duration was 6.6 years, and mean levodopa equivalent daily dose was 721.1 mg/day. At week 18, significant improvements from baseline were seen for the co-primary endpoints, mean daily “off” time (− 1.3 ± 2.4 h, p < 0.001) and quality of life (QoL) based on PDQ-39 summary index (− 2.7 ± 10.3, p < 0.001), Moreover, significant improvements were seen in motor symptoms and motor complications (MDS-UPDRS part 3 and 4), daily “on” time without dyskinesia (all p < 0.001) and pain (KPPS; p = 0.013). TEAEs occurred in 40.2