Multiple system atrophy (MSA) is a clinically heterogeneous disorder. Conventional motor phenotype-based classification provides limited prognostic information. Previously, we identified data-driven subtypes of early-stage MSA using a latent class analysis (LCA) that incorporated both motor and non-motor features. However, the prognostic significance of these subtypes remains unclear. We analyzed the survival outcomes in a previously reported cohort of 61 patients with probable or possible MSA enrolled within three years of motor symptom onset. Patients were classified according to LCA-derived subtypes and dichotomized into an extensive or restricted dysautonomia group based on shared autonomic profiles. Overall survival was assessed using Kaplan–Meier analysis and compared using the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) with progressive adjustments for the age at onset, sex, baseline disease severity (Unified Multiple System Atrophy Rating Scale, UMSARS Part I), and disease duration at enrollment. Survival analysis was performed in 60 patients, 47 of whom died by the end of follow-up. The extensive dysautonomia group showed a significantly shorter median survival than the restricted group (6.0 vs. 7.0 years; log-rank p = 0.008). After adjusting for the age at onset and sex, the restricted group had a lower risk of mortality (adjusted HR: 0.538, 95

The antihistamine astemizole has shown disease-modifying effects in several preclinical disease models of Parkinson’s disease (PD). Astemizole also interacts with an anomalous aggregation of Alzheimer’s disease-related amyloid-β (Aβ) peptide and has inhibitory activity on the human prion protein PrPSc. We hypothesized that the proposed preclinical benefits of astemizole on PD can be associated with the attenuation of pathological α-synuclein (α-syn) aggregation. We tested the effects of astemizole on the fibrillation processes of amyloid peptides using thioflavin T aggregation monitoring, Congo red spectral analysis, cell viability study, and transmission electron microscopic imaging. We found that astemizole did not inhibit α-syn aggregation in vitro even at a high molar ratio but inhibited the assembly of Aβ aggregates. Our results suggest that the inhibitory effect of astemizole on amyloid formation is target-protein selective, and the proposed beneficial effects of this compound observed in translational PD models might not be due to its ameliorating effects on α-syn aggregation.

OBJECTIVE:Parkinson's disease (PD) patients often find it difficult to visit hospitals because of motor symptoms, distance to the hospital, or the absence of caregivers. Telemedicine is one way to solve this problem.METHODS:We surveyed 554 PD patients from eight university hospitals in Korea. The questionnaire consisted of the clinical characteristics of the participants, possible teleconferencing.METHODS:, and preferences for telemedicine.RESULTS:A total of 385 patients (70%) expressed interest in receiving telemedicine. Among them, 174 preferred telemedicine whereas 211 preferred in-person visits. The longer the duration of disease, and the longer the time required to visit the hospital, the more patients were interested in receiving telemedicine.CONCLUSION:This is the first study on PD patients' preferences regarding telemedicine in Korea. Although the majority of patients with PD have a positive view of telemedicine, their interest in receiving telemedicine depends on their different circumstances.

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.

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.

BACKGROUND:This study aimed to investigate 1) long-term outcomes of deep brain stimulation (DBS), such as mortality after DBS as well as the causes of death, 2) demographic and socioeconomic factors influencing mortality, and 3) comorbidities affecting mortality after DBS in patients with Parkinson's disease (PD).METHODS:This study analyzed the National Health Insurance Service-National Health Information Database. Data on patients with PD diagnosis codes from 2002 to 2019 were extracted and analyzed. Data on the causes of death were obtained by linking the causes of death to data from Statistics Korea. The Kaplan-Meier method with the log-rank test was used for survival analysis. Multivariate Cox regression analyses were used to estimate hazard ratios (HRs) and their 95% confidence intervals. Regarding comorbidities such as PD dementia and fracture, which did not satisfy the assumption for the proportional HR, time-dependent Cox analysis with the Mantel-Byar method was used.RESULTS:From 2005 to 2017, among 156,875 patients diagnosed with PD in Korea, 1,079 patients underwent DBS surgery, and 251 (23.3%) had died by 2019. The most common cause of death (47.1%) was PD. In the multivariate Cox regression analysis, the higher the age at diagnosis and surgery, the higher the mortality rate. The men and medical aid groups had significantly higher mortality rates. PD dementia and fracture were identified as risk factors for mortality.CONCLUSION:Older age at diagnosis and surgery, being male, the use of medical aid, and the comorbidity of dementia and fractures were associated with a higher risk of mortality after DBS in patients with PD. Neurologists should consider these risk factors in assessing the prognosis of PD patients undergoing DBS.

Background Studies of secondary movement disorder (MD) caused by cerebrovascular diseases have primarily focused on post-stroke MD. However, MD can also result from cerebral artery stenosis (CAS) without clinical manifestations of stroke. In this study, we aimed to investigate the clinical characteristics of MD associated with CAS. Materials and Methods A nationwide multicenter retrospective analysis was performed based on the data from patients with CAS-associated MDs from 16 MD specialized clinics in South Korea, available between January 1999 and September 2019. CAS was defined as the >50% luminal stenosis of the major cerebral arteries. The association between MD and CAS was determined by MD specialists using pre-defined clinical criteria. The collected clinical information included baseline demographics, features of MD, characteristics of CAS, treatment, and MD outcomes. Statistical analyses were performed to identify factors associated with the MD outcomes. Results The data from a total of 81 patients with CAS-associated MD were analyzed. The mean age of MD onset was 60.5 ± 19.7 years. Chorea was the most common MD (57%), followed by tremor/limb-shaking, myoclonus, and dystonia. Atherosclerosis was the most common etiology of CAS (78%), with the remaining cases attributed to moyamoya disease (MMD). Relative to patients with atherosclerosis, those with MMD developed MD at a younger age (p < 0.001) and had a more chronic mode of onset (p = 0.001) and less acute ischemic lesion (p = 0.021). Eight patients who underwent surgical treatment for CAS showed positive outcomes. Patients with acute MD onset had a better outcome than those with subacute-to-chronic MD onset (p = 0.008). Conclusions This study highlights the spectrum of CAS-associated with MD across the country. A progressive, age-dependent functional neuronal modulation in the basal ganglia due to CAS may underlie this condition.

Introduction: Patients with multiple system atrophy (MSA) are conventionally identified as having MSA-P (prominent parkinsonism) or MSA-C (prominent cerebellar ataxia) based on their predominant motor manifestations. The objective of the present study was to conduct latent class analysis (LCA) of various motor and nonmotor symptoms in early MSA to characterize data-driven subgroups. Methods: Sixty-one probable or possible MSA patients with disease durations of 3 years or less were included prospectively. LCAs were performed to identify similar clinical subgroups giving even weights to a wide range of MSA motor and nonmotor features. We ran latent models of up to 6 class solutions; the overall model fit was evaluated based on the parsimony of the derived classes, the fit indices, and clinical interpretability. Results: The LCA outcome supported categorization of at least three subgroups of patients with early MSA: the largest class 1, labeled "moderate parkinsonism + extensive dysautonomia", included approximately half of our study patients and showed marked autonomic dysfunction with a burden of parkinsonism. The two other classes, class 2 "predominant parkinsonism + limited dysautonomia" and class 3 "predominant cerebellar symptoms + limited dysautonomia", showed marked core motor features (parkinsonism or cerebellar symptoms) with generally mild dysautonomia. Conclusions: To our knowledge, this is the first data-driven identification of disease subtypes covering various symptom constellations in early MSA (<3 years from motor symptom onset). The present LCA result did not replicate the conventional motor classification and supported the heterogeneity within MSA-P and MSA-C subtypes.

Traumatic brain injury (TBI) is one of the leading causes of death in the pediatric population in Korea. In addition, it can cause disability in children and adolescents, with physical and mental consequences. This causes a substantial burden on the health care system and occurs globally and not just in Korea. We searched and reviewed current data on the epidemiologic characteristics of pediatric TBI in Korea. Our review provides the recent epidemiological trend mainly focusing on incidence and mortality along with worldwide reported data. This review will be helpful to understand the global epidemiology of pediatric TBI and its differences between countries.

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive lipid storage disorder caused by 27-hydroxylase deficiency. We report the clinical characteristics of six Korean CTX patients. The median age of onset was 22.5 years, the median age at diagnosis was 42 years, and the diagnostic delay was 18.1 years. The most common clinical symptoms were tendon xanthoma and spastic paraplegia. Four of five patients exhibited latent central conduction dysfunction. All patients carried the same mutation in CYP27A1 (c.1214 G>A [p.R405Q]). CTX is a treatable neurodegenerative disorder; however, our results revealed that patients with CTX in Korea might receive the diagnosis after a prolonged delay.

Objectives:4H leukodystrophy is a rare autosomal recessive hypomyelinating disorder characterized by several combinations of motor dysfunction, abnormal dentition, and ophthalmic and endocrine abnormalities. To date, only a single Korean case report of pediatric leukodystrophy caused by the POLR1C sequence variation has been published, while there are no reports on the POLR3B, POLR3A, or POLR3K variants.Methods:Genetic tests of Korean sibling pairs with primary amenorrhea due to normosmic isolated hypogonadotropic hypogonadism and cognitive or behavioral symptoms were performed by whole-exome sequencing (WES). The WES results were validated by direct Sanger sequencing.Results:We identified biallelic variations in the POLR3B gene of p.Tyr685* and p.Tyr746Cys, which have not been associated with 4H leukodystrophy. Both sequence variants lie in the hybrid-binding domain of the protein RPC2. The protein structure analysis predicted that cysteine substitution of the phylogenetically conserved amino acid tyrosine can cause destabilization.Discussion:The siblings reported are the first POLR3B-related hypomyelinating leukodystrophy cases in Korea. Our report expands the mutational spectrum of 4H leukodystrophy and suggests that it is mandatory to consider its diagnostic possibility in adult patients presenting with primary amenorrhea and mild cognitive or behavioral symptoms.

Background: Depression and anxiety are prevalent and can cause suffering in patients with Parkinson’s disease (PD). The Korean version of the Hospital Anxiety and Depression Scale (K-HADS) has been widely used to assess depression and anxiety symptoms in Korean patient with PD. The present study aimed to assess the reliability and validity of the K-HADS using Rasch measurement analysis.Methods: A total of 106 PD patients (54 males, 52 females) who met the diagnostic criteria of the United Kingdom Brain Bank were recruited. Unidimensionality, the Rasch model fit, response category functioning, patient-item distribution, and the separation reliability of the K-HADS depression (K-HADS-D) and anxiety (K-HADS-A) subscales were statistically evaluated.Results: The mean K-HADS-D and K-HADS-A scores were 8.08±4.69 (mean±standard deviation) and 5.44±4.18, respectively. Cronbach’s α coefficients of the K-HADS-D and K-HADS-A were 0.82 and 0.83. The Rasch analysis revealed that the K-HADS-D and K-HADS-A showed unidimensionality and no disordered functioning was observed in the 4-point polytomous scale. However, both K-HADS-D and K-HADS-A exhibited suboptimal separation reliability, while the K-HADS-A showed inadequate scale targeting with floor effect.Conclusions: The present study comprises the first validation of the K-HADS using the Rasch measurement model, suggesting that the K-HADS-D and K-HADS-A are clinimetrically acceptable and reliable scales for use in Korean patients with PD. However, the moderate person separation indices implicate the relatively low discriminatory ability of the K-HADS in our study patients.

Assessing patient goals is crucial in understanding patient centered outcomes and satisfaction. However, patient goals may change throughout treatment. Our objective is to identify the changes in patient-selected goals of Parkinson's disease (PD) patients undergoing bilateral subthalamic nucleus deep brain stimulation (STN-DBS) and examine the relationship among patient-selected goal achievement, standard DBS outcome measures, and overall patient satisfaction. Seventy-five patients undergoing bilateral STN-DBS listed three patient-selected goals before surgery. After six months, patients were asked to restate the three goals and to rate the degree of goal achievement and the overall satisfaction of surgery. The three most frequently selected goals were "dyskinesia", "gait disorder", and "medication off duration". After six months, 80.0% of patients could not accurately recall their pre-DBS goals. "Dyskinesia" was the most consistently selected goal, more patients selected "tremor" and "less medication" at post-DBS compared to pre-DBS, and less patients selected "gait disorder" at post-DBS compared to pre-DBS. 74.7% of patients reported overall satisfaction by stating they were "very much" or "much better after surgery". Patient satisfaction significantly correlated with goal achievement (r = 0.640; p < 0.001). Interestingly, change in UPDRS motor scores did not correlate with patient satisfaction (r = 0.100; p = 0.395). Although recalled goals do not accurately represent the pre-surgical goals, the achievement score for recalled goals significantly correlated with patient satisfaction. Patient goals change due to many reasons. Therefore, follow-up patient counseling to discuss goals and outcomes is important in improving patient satisfaction after STN-DBS.

Background and Purpose Impulse-control disorder is an important nonmotor symptom of Parkinson's disease (PD) that can lead to financial and social problems, and be related to a poor quality of life. A nationwide multicenter prospective study was performed with the aim of validating the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (K-QUIP-RS). Methods The K-QUIP-RS was constructed using forward and backward translation, and pretesting of the prefinal version. PD patients on stable medical condition were recruited from 27 movement-disorder clinics. Participants were assessed using the K-QUIP-RS and evaluated for parkinsonian motor and nonmotor statuses and for PD-related quality of life using a predefined evaluation battery. The test retest reliability of the K-QUIP-RS was assessed over an interval of 10-14 days, and correlations between the KQUIP-RS and other clinical scales were analyzed. Results This study enrolled 136 patients. The internal consistency of the K-QUIP-RS was indicated by a Cronbach's a coefficient of 0.846, as was the test retest reliability by a Guttman split-half coefficient of 0.808. The total K-QUIP-RS score was positively correlated with the scores for depression and motivation items on the Unified PD Rating Scale (UPDRS), Montgomery-Asberg Depression Scale, and Rapid-Eye-Movement Sleep-Behavior-Disorders Questionnaire. The total K-QUIP-RS score was also correlated with the scores on part II of the UPDRS and the PD Quality of Life-39 questionnaire, and the dopaminergic medication dose. Conclusions The K-QUIP-RS appears to be a reliable assessment tool for impulse-control and related behavioral disturbances in the Korean PD population.

Background and Purpose This study aimed to determine the clinimetric properties of the Korean version of Parkinson's Disease Sleep Scale-2 (K-PDSS-2) and whether distinct subtypes of sleep disturbance can be empirically identified in patients with Parkinson's disease (PD) using the cross-culturally validated K-PDSS-2. Methods The internal consistency, test-retest reliability, scale precision, and convergent validity of K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities. Results The total K-PDSS-2 score was 11.67 +/- 9.87 (mean +/- standard deviation) at baseline and 12.61 +/- 11.17 at the retest. Cronbach's a coefficients of the total K-PDSS-2 scores at baseline and follow-up were 0.851 and 0.880, respectively. The intraclass correlation coefficients over the 2-week study period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated with health-related quality of life measures and other corresponding nonmotor scales. LCA revealed three distinct subtypes of sleep disturbance in the study patients: "less-troubled sleepers:," "PD-related nocturnal difficulties," and "disturbed sleepers". Conclusions K-PDSS-2 showed good clinimetric attributes in accordance with previous studies that employed the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. This study has further documented the first application of an LCA approach for identifying subtypes of sleep disturbance in patients with PD.

The State-Trait Anxiety Inventory (STAI), composed of two 20-item subscales (STAI-state and STAI-trait), has been increasingly used to assess anxiety symptoms in patients with Parkinson's disease (PD). However, the clinimetric attributes of the STAI under the statistical framework of the item-response theory (IRT) have not been fully elucidated within this population to date. We performed an IRT-based Rasch analysis of the STAI outcomes of patients with de novo PD from the Parkinson's Progression Markers Initiative database. The unidimensionality, Rasch model fit, scale targeting, separation reliability, differential item functioning, and response category utility of the STAI were statistically evaluated. A total of 326 (209 males, 117 females) patients without cognitive dysfunction were enrolled in our study. The original versions of the STAI-state and STAI-trait had acceptable separation reliability but lacked appropriate response category functioning, exhibited scale off-targeting, and several items demonstrated poor fit to the Rasch model. The response categories were reduced from four to three, and the rescored three-point TASI-trait demonstrated a marked improvement in clinimetric properties without a significant impact on unidimensionality and separation reliability. The rescored three-point version of the STAI-state required the additional removal of four misfitting items in order to improve the Rasch model fit. To our knowledge, this is the first study to assess the measurement properties based on the IRT of the STAI in patients with PD. Our Rasch analysis identified the components requiring possible amendments in order to improve the clinimetric attributes of the STAI.

Background: Sleep-related problems in Parkinson’s disease (PD) have received greater attention in recent years due to their clinical influence on morbidity, disability, and the health-related quality of life (HRQoL) of patients. This study aimed to evaluate the clinimetric properties of the Korean version of the Parkinson’s Disease Sleep Scale-2 (K-PDSS-2), and to analyze whether distinct sleep disturbance subtypes could be empirically identified in patients with PD based on the cross-culturally validated K-PDSS-2. Methods: The internal consistency, test-retest reliability, scale precision, and convergent validity of the K-PDSS-2 were assessed in a nationwide, multicenter study of 122 patients with PD. Latent class analysis (LCA) was used to derive subgroups of patients who experienced similar patterns of sleep-related problems and nocturnal disabilities. Results: The mean total K-PDSS-2 scores were 11.67 ± 9.87 (mean ± standard deviation) at baseline, and 12.61 ± 11.17 upon follow up testing. The Cronbach’s α coefficients of the total K-PDSS-2 score at baseline and at follow up testing were 0.851 and 0.880 respectively. Intraclass correlation coefficient over the 2-week period ranged from 0.672 to 0.848. The total K-PDSS-2 score was strongly correlated to HRQoL measures and other corresponding nonmotor scales. LCA indicated three distinct sleep disturbance classes in the study patients, namely “less troubled sleepers”, “PD-related nocturnal difficulties”, and “disturbed sleepers”. Conclusions: The K-PDSS-2 showed good clinimetric attributes in accordance with prior studies that were using the original version of the PDSS-2, therefore confirming the cross-cultural usefulness of the scale. Further, this study documents the first application of an LCA approach for identifying sleep disturbance subtypes in patients with PD. Keywords: Parkinson’s disease; sleep; PDSS-2; validity; reliability; Korean version; latent class analysis.

Background:Multiple system atrophy (MSA) patients present a variety of symptoms other than autonomic dysfunctions, parkinsonism, and cerebellar ataxia. The aim of this study was to evaluate the frequency of various motor and non-motor symptoms including so-called "red flags" in patients with early MSA and to determine whether the frequency of these symptoms was different between the parkinsonian (MSA-P) and cerebellar (MSA-C) subtypes.Methods:Sixty-one probable or possible MSA patients with disease duration of 3 years or less were included. Patients were classified into MSA-P, MSA-C, and MSA-PC. The frequency of 13 features including various motor and non-motor symptoms that commonly occur in MSA was assessed.Results:Dysarthria was the most prevalent feature (98.4%) followed by sexual dysfunction (95.1%). Probable REM sleep behavior disorder was present in 90.2%. The frequency of constipation (82.0%), dysphagia (68.9%), and snoring (70.5%) was also high. Stridor was present in 42.6% and more common in MSA-C than in MSA-P.Conclusions:Increasing awareness of various motor and non-motor symptoms may assist clinicians to make an early, accurate diagnosis and to improve management of patients with MSA. We suggest that the diagnostic accuracy can be improved if these features are appropriately reflected in the new diagnostic criteria for MSA.

BACKGROUND Dyskinesia, wearing off (WO) and freezing of gait (FOG) are troublesome complications degrading quality of life in the course of Parkinson's disease (PD). OBJECTIVE This study evaluated the gross chronological trend of 4 motor complications - peak dose dyskinesia (PDSK), diphasic dyskinesia (DDSK), WO and FOG in a large PD population with stratification by age at disease onset according to the PD duration. METHODS The motor complications of 1212 Korean PD patients were analyzed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS PDSK and WO appeared first as motor complications and showed accelerated development around the 5 year-PD-duration, while DDSK showed a rather constant development over time and FOG developed around the 10 year-disease duration at an accelerated rate (p <  0.001). A younger age at PD onset predicted an earlier appearance of PDSK, DDSK and WO (p <  0.001), while an older age at onset (≥60 years) was a predictor for FOG (p = 0.014). CONCLUSION Motor complications developed with a distinguishing inclination over the PD duration. This study provides insight into the chronological trend of motor complications in PD at a glance.