Dallah Yoo

Progressive Supranuclear Palsy with Coexisting Chronic Traumatic Encephalopathy and Multiple Tauopathies in a Non-athlete with Recurrent Falls

Development and Validation of the 9-item Parkinson’s Disease Screening Questionnaire

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.

Objective Exercises have been proposed as adjuvants for the treatment of Parkinson’s disease (PD); however, responses to exercise interventions have shown inconsistent results. We investigated the clinical factors associated with improvements in motor deficits after exercise.Methods A total of 85 patients with PD were enrolled from five tertiary hospitals and classified into four exercise groups: home exercise, strength training, Tai Chi, and yoga groups. Clinical measurements of the motor and nonmotor features of patients with PD were performed at baseline and 12 weeks after the exercise intervention. We employed principal component analysis (PCA) to reduce variables into ten factors and then examined associations of baseline characteristics with percentage improvement in the Movement Disorder Society sponsored Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) score via a Bayesian regression model.Results In the multivariate Bayesian regression model including ten PCA-derived factors, the percentage improvement in the MDS-UPDRS III score was associated with factors including prominent motor deficits (posterior interval [mean±standard deviation]: 2.5±1.5) and nonmotor symptoms such as depression, anxiety, and subjective memory impairment (3.3±1.7). Another factor related to functional impairments in gait and postural control was associated with less improvement after the exercise intervention (-3.9±1.7). According to the subgroup analyses, motor features were associated with improvements in the home exercise and strength training groups, whereas mood disturbance, fatigue, and subjective cognitive impairment were related to changes in the home exercise and Tai Chi groups.Conclusion Our results suggest that the individual phenotypes of patients with PD may be associated with clinical improvement following exercise.

Objectives: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by the progressive narrowing of arteries at the base of the brain, forming abnormal collateral vascular networks. While vascular parkinsonism is noted in MMD, its link to Parkinson's disease (PD) has not been explored. We aimed to determine whether the risk of PD is increased in patients with MMD and to identify the potential role of the RNF213 gene. Methods: We report two cases of PD with a history of MMD associated with the Arg4810Lys variant of RNF213 . Using the Korean National Health Insurance Service database, we studied the association between MMD and subsequent PD risk using Cox proportional hazards regression analysis. Moreover, we explored the interaction between α‐synuclein and RNF213 proteins by overexpressing SNCA and RNF213 in SH‐SY5Y cells. Furthermore, we confirmed the proximity of Lewy pathology and RNF213 proteins in postmortem brain tissues from three patients with PD and age‐matched controls. Results: Among 16,830 patients aged ≥ 40 with MMD, 3415 were enrolled, excluding those with prior PD or stroke, along with a matched control group of 33,974. The analysis revealed an increased PD risk in patients with MMD (hazard ratio = 4.45 [3.40–5.82], p < 0.0001). Overexpression of RNF213 resulted in cytoplasmic inclusions, which were worsened by the co‐expression of SNCA and the Arg4810Lys variant of RNF213. Histological studies confirmed the co‐localization of α‐synuclein aggregates and RNF213 proteins in PD brain tissues. Interpretation: This study confirms the heightened PD risk in patients with MMD and suggests a pathophysiological link through α‐synuclein and RNF213 interactions.

Objective Exercise is a critical nonpharmacological intervention for Parkinson’s disease (PD); however, comparative evidence on the efficacy of different exercise modalities is limited. This study aimed to compare the effects of tai chi, strength training, yoga, and home-based exercises on motor function in patients with PD.Methods In this multicenter, open-label, randomized clinical trial, 99 patients with PD were allocated to one of four exercise interventions: tai chi, strength training, yoga, or home-based exercises. Each intervention consisted of 12 weeks of supervised sessions, followed by 12 weeks of independent practice. The primary outcomes included the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part III and timed up-and-go (TUG) test parameters. The assessed secondary outcomes included physical activity (measured via short physical performance battery and the 6-minute walking test [6MWT]), balance (measured via the Mini-BEST), and freezing of gait (measured via the New Freezing of Gait Questionnaire).Results Home exercise and tai chi demonstrated significant improvements in the MDS-UPDRS Part III scores over 24 weeks. The 6MWT was improved by home exercises and tai chi; additionally, the Mini-BEST test scores were enhanced by strength exercises and yoga. The total duration and forward movement of the TUG test, as well as the turning duration measured via the wearable sensor, were markedly improved in the yoga group.Conclusion Our results support the notion that various types of adherence to and outcomes of exercise can be observed in real-world settings, even though the effectiveness of exercise is well established. These findings highlight the importance of tailoring exercise regimens by considering individual patients in PD management.

The advance care planning was enacted with the intention of facilitating a dignified death. However, its original purpose often falls short for elderly patients suffering from severe neurological disorders. This review examines the practical challenges observed in clinical settings, focusing on how the current system may not adequately apply to, or in some cases even infringes upon the rights of, elderly patients with severe neurological conditions. It highlights critical issues such as the absence of decision-making capacity due to cognitive decline or loss of consciousness, the limited accessibility and utilization of institutional ethics committees, and the subjective prognosis judgments made by medical professionals. This paper aims to provide patients, their families, and healthcare providers with a clear understanding of the current system’s limitations, fostering awareness of the dilemmas and problems that arise in the process of making life-sustaining treatment decisions.