Search

Most previous genome-wide association studies (GWASs) on Parkinson’s disease (PD) focus on the European population. There are several sex-specific clinical differences in PD, but little is known about its genetic background. In this study, we aimed to perform an ethnicity-specific, and sex-specific GWAS on PD in the Korean population. A total of 1,050 Korean PD patients and 5,000 controls were included. For primary analysis, we performed a GWAS using a logistic additive model adjusted for age and sex. Same statistical models were also applied to sex-specific analyses. Genotyping was performed using a customized microarray chip that is optimal for the Korean population. Nine single nucleotide polymorphisms (SNPs) including four in the SNCA locus and three from the PARK16 locus were associated with PD in Koreans. The rs34778348 in the LRRK2 locus showed a strong association, though failed to pass cluster quality control. There were no notable genome-wide significant markers near the MAPT or GBA loci. In the female-only analysis, rs34778348 in LRRK2 and the four other SNPs in the SNCA showed strong association with PD. In the male-only analysis, no SNP surpassed the genome-wide significance threshold under Bonferroni correction; however, the most significant signal was rs708726 in the PARK16 locus. This ethnicity- and sex-specific GWAS on PD implicates the pan-ethnic effect of SNCA, universal but East-Asian inclined effect of PARK16, East Asian-specific role of LRRK2 G2385R variants, and the possible disproportionate effect of SNCA and PARK16 between sexes for PD susceptibility. These findings suggest the different genetic contributions to sporadic PD in terms of ethnicity and sex.

McLeod syndrome is a rare X-linked recessive genetic disorder that is caused by mutations of the XK gene. It is one of the core neuroacanthocytosis syndromes. We report the case of a 67-year-old man who presented to Kyungpook National University Hospital in the Republic of Korea with progressive worsening of generalized chorea and dystonia. He had no recognized family history of neurologic illness. A peripheral blood smear showed increased acanthocytes. His serum creatine kinase levels were 894 U/L. A brain MRI showed atrophy of the bilateral striatal nuclei. An F-18 F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane PET/CT showed moderately decreased dopamine transporter uptake in the putamen and severely decreased uptake in the caudate nucleus. An F-18 fludeoxyglucose PET/CT demonstrated markedly decreased metabolism at the caudate nucleus and the putamen. Whole exome sequencing revealed hemizygous pathogenic mutations of the XK gene (c.856_860delCTCTA;p.Leu286TyrfsTer16). We believe that these findings provide useful information regarding the clinical features of individuals with McLeod syndrome.

Introduction Nocturnal stridor, a life-threatening condition linked to respiratory failure and sudden death during sleep, is a serious issue in patients with multiple system atrophy (MSA). However, little is known about polysomnographic findings and clinical features of MSA patients with nocturnal stridor. Hence, we investigated video-polysomnography (VPSG) findings and clinical features associated with nocturnal stridor in patients with MSA. Methods We retrospectively analyzed the clinical data of patients with MSA (n = 49) who underwent overnight VPSG for the evaluation of sleep-disordered breathing. The presence of nocturnal stridor was confirmed based on overnight VPSG findings. Clinical data, including VPSG findings and clinical features, were compared between MSA patients with and without nocturnal stridor. Results Nocturnal stridor was present in 31 (63.3%) patients with MSA. Patients with stridor showed significantly higher apnea-hypopnea, respiratory disturbance, and oxygen desaturation indices than those without stridor (P = 0.024, P = 0.049, and P = 0.006, respectively). Patients with stridor had more severe axial motor features, more impaired activities of daily living, and longer disease duration than those without stridor (P = 0.012, P = 0.036, and P = 0.003, respectively). However, there were no significant between-group differences in sex, age at disease onset, MSA subtype, parkinsonian features, cerebellar ataxia, residual urine volume, or systolic and diastolic blood pressure change. Conclusions MSA with nocturnal stridor is related to higher apnea indices in conjunction with higher O2 desaturation index, more severe axial motor features, more impaired activities of daily living, and longer disease duration.

Introduction Although autonomic dysfunction is the prominent clinical feature in multiple system atrophy (MSA), little is known about the pupillary autonomic aspect of MSA. We aimed to evaluate pupillary autonomic function in MSA patients using dynamic pupillometry, which can quantify the pupillary light reflex. Methods Dynamic pupillometry parameters were compared in 21 MSA patients and 21 healthy controls. Pupillometric parameters were correlated with total Unified Multiple System Atrophy Rating Scale (UMSARS) scores and autonomic symptom severity. Results Average constriction (p = 0.034) and dilation (p = 0.003) velocities were significantly slowed in MSA patients compared with controls. Total UMSARS correlated with the average constriction (r = −0.527, p = 0.017) and maximum constriction (r = −0.658, p = 0.003) velocities. Autonomic symptom severity correlated with average constriction (r = −0.544, p = 0.013), maximum constriction (r = −0.607, p = 0.005) and average dilation (r = −0.499, p = 0.025) velocities. Conclusion Dynamic pupillometry may provide useful information about pupillary autonomic dysfunction, which correlated with the clinical severity, in patients with MSA.

Background Alpha-synuclein (α-Syn) immunostaining in the enteric nervous system (ENS) has been investigated to determine the role of diagnostic biomarker of Parkinson's disease (PD). However, determining factors for alpha-synuclein (α-Syn) deposition in the ENS of humans are still unclear. We aimed to investigate a possible association between SNCA variants and the presence of α-Syn immunostaining in the ENS in patients with PD and healthy individuals. Methods The study subjects consisted of 38 patients with PD and 46 healthy individuals. α-Syn immunohistochemistry was performed for gastric and colonic mucosal tissues of patients with PD and controls. Mucosal biopsy tissues of the ENS were obtained using standard biopsy forceps by endoscopic gastroduodenoscopy or colonoscopy. Two variants within the SNCA gene (the single nucleotide polymorphism [SNP] rs11931074 and the microsatellite REP1) were genotyped. Results In patients with PD, the rs11931074 (G allele) was significantly associated with the presence of α-Syn immunostaining in the ENS (OR = 5.96, 95% CI = 1.70–20.97, P = 0.01). In an interaction analysis, SNP rs11931074–PD status interaction was significantly associated with positive α-Syn immunostaining in the ENS (OR = 7.33, 95% CI = 1.58–33.88, P = 0.01). Longer SNCA REP1 alleles were not associated with positive α-Syn immunostaining in the ENS. Conclusion This exploratory study demonstrated that α-Syn deposition in the ENS may be associated with SNCA variants in patients with PD.

The outbreak of the COVID-19 pandemic is a substantial threat to the health of all populations worldwide, and old age is a robust risk factor for poor prognosis of COVID-19 infection. To reduce the fatality rate of COVID-19 infection, further understanding of elderly patients with COVID-19 is necessary. We aimed to investigate the prognostic factors in elderly patients with COVID-19. This was a multicenter and retrospective study. Overall, 340 elderly patients with COVID-19 were enrolled in 3 hospitals in Daegu, South Korea. Death and severe pneumonia requiring oxygen treatment were defined as poor clinical outcomes. Of the patients studied, 15% died and 35.2% were classified as having severe pneumonia. In binary logistic regression analysis, activities of daily living (ADL) impairment, fever during hospitalization, initial infiltration on chest radiograph, and initial increased C-reactive protein (CRP) were significantly associated with severe pneumonia (OR = 5.33, p < 0.001; OR = 3.2, p = 0.002; OR = 2.32, p = 0.044; and OR = 1.33, p < 0.001, respectively). ADL impairment, comorbidity, fever during hospitalization, and initial increased CRP were significantly associated with death (OR = 7.13, p < 0.001; OR = 3.28, p = 0.005; OR = 3.15, p = 0.032, and OR = 1.18, p < 0.001, respectively). ADL impairment, fever, and initial CRP were poor prognostic factors in elderly patients with COVID-19. Understanding these poor prognostic factors is necessary to control the disease in elderly patients.

Objective To investigate the efficacy of levodopa/carbidopa/entacapone (LCE) at bedtime for treating sleep disturbance in patients with Parkinson’s disease (PD) with motor fluctuations. 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.

Introduction While metals have been implicated in the pathophysiology of Parkinson's disease (PD), the clinical evidence is scarce. Further, the contribution of metals for the risk or clinical presentation of PD remains to be explored. Methods To investigate the associations between the level of metals in blood serum and PD risk or clinical presentation, including sex-related differences, we studied 325 PD patients and age- and sex-matched 304 controls. We collected clinical data of the PD patients, including age at onset, PD duration, levodopa-equivalent dose (LED), Hoehn and Yahr stage (H-Y stage), presence of motor fluctuation, levodopa-induced dyskinesia (LID), freezing of gait, hallucination, and Mini-Mental State Examination (MMSE) score. Iron, copper, and zinc levels in serum were assayed by inductively coupled plasma mass spectrometry. Statistical analyses were performed to determine the sex-related differences in metal levels. Results Among the three metal elements tested, serum copper levels showed significant correlations with PD risk or clinical presentation. Higher copper levels were associated with a decreased PD risk. Higher copper or lower iron levels were associated with the risk of LID in women. Serum copper levels were negatively correlated with MMSE scores in PD patients. Conclusions This clinical study suggests significant associations between serum metal levels and PD risk or essential clinical features, demonstrating the possible roles of metals in PD pathogenesis or symptom development.

Dementia is one of the most disabling nonmotor symptoms of Parkinson’s disease (PD). However, the risk factors contributing to its development remain unclear. To investigate genetic variants associated with dementia in PD, we performed microarray genotyping based on a customized platform utilizing variants identified in previous genetic studies. Microarray genotyping was performed in 313 PD patients with dementia, 321 PD patients without dementia, and 635 healthy controls. The primary analysis was performed using a multiple logistic regression model adjusted for age and sex. SNCA single nucleotide polymorphism (SNP) rs11931074 was determined to be most significantly associated with PD (odds ratio = 0.66, 95% confidence interval = 0.56–0.78, p = 7.75 × 10−7). In the analysis performed for patients with PD only, MUL1 SNP rs3738128 (odds ratio = 2.52, 95% confidence interval = 1.68–3.79, p = 8.75 × 10−6) was found to be most significantly associated with dementia in PD. SNPs in ZHX2 and ERP29 were also associated with dementia in PD. This microarray genomic study identified new loci of MUL1 associated with dementia in PD, suggesting an essential role of mitochondrial dysfunction in the development of dementia in patients with PD.

Objective Risk factors of infection after deep brain stimulation (DBS) surgery in patients with Parkinson disease (PD) have been controversial. We aimed to investigate the clinical characteristics and risk factors of infection after DBS surgery in PD patients. Methods We retrospectively investigated 246 consecutive DBS surgeries in 169 advanced PD patients. Clinical data were collected and analyzed to clarify the clinical characteristics associated with infection after DBS surgery. Multivariate logistic regression analysis was used to assess risk factors for infection after DBS surgery. Results Infection occurred in 5% of all DBS surgeries and in 7% of all PD patients who received DBS surgery. Most infections (75%) occurred within 3 months after DBS surgery but it also occurred 21 months after DBS surgery. Gram-positive bacteria were the most common pathogens (75%). Infection after DBS surgery was associated with short period of prophylactic antibiotic therapy (OR = 0.62, 95% CI = 0.45–0.85, P = 0.002) and intensive care unit (ICU) management immediate after DBS surgery (OR = 5.43, 95% CI = 1.12–26.45, P = 0.036). Conclusion Our study suggests that short period of prophylactic antibiotic therapy and ICU management after surgery may increase the risk of infection in PD patients who received DBS surgery.

Introduction Long-term efficacy and safety of subthalamic nucleus deep brain stimulation (STN DBS) in patients with young-onset Parkinson's disease (YOPD) and late-onset PD (LOPD) (i.e. motor symptom initial appearance at ages ≤40 and > 40 years, respectively) was compared to identify relationships between PD onset age and the efficacy of DBS. Methods Statistical analyses compared specific motor and non-motor features among 13 patients with YOPD and 11 with LOPD. Medication reduction patterns and dyskinesia severity scores at baseline and after 1, 3, 5, and 10 years of follow-up were also analyzed using a repeated measures ANOVA tests. Lastly, a correlation analysis identified relationships between the impact of DBS settings (volume of activated tissue) and levodopa equivalent daily dose (LED), dyskinesia severity scores, Unified Parkinson's Disease Rating Scale (UPDRS) part III, and UPDRS part II (disability) scores. Results Ten years after DBS surgery, the reduction of LED from baseline (85.9 ± 592.6 mg versus 623.2 ± 464.9 mg; p = .023) and levodopa-induced dyskinesia (LID) scores (Unified Dyskinesia Rating Scale [UDysRS] parts III items 16–22; 1.6 ± 2.8 versus 5.5 ± 4.1; p = .013) were significantly lower in YOPD patients than LOPD patients. There were no significant differences between the two groups regarding UPDRS part III score improvement in response to levodopa, psychosis occurrence, or adverse effects. Conclusion Ten years after STN DBS surgery, LOPD patients showed greater LED reduction, and YOPD patients showed greater LID improvement, although the general long-term outcomes were similar between YOPD and LOPD patients.

Background Post-pump chorea and progressive-supranuclear palsy (PSP)-like syndrome after aortic surgery are 2 distinct movement disorders following major cardiac surgeries. Cases We herein report 3 patients with movement disorders that developed after major cardiac surgeries. Two patients developed post-pump chorea after pulmonary endarterectomy, and 1 further case developed PSP-like syndrome after aortic replacement surgery. The 2 conditions share several common aspects. Both are preceded by surgeries that undergo cardiopulmonary bypass and deep hypothermia circulatory arrest procedures. Most cases present with biphasic course. However, post-pump chorea occurs in all age populations after any surgeries that undergo deep hypothermia circulatory arrest, whereas PSP-like syndrome is reported exclusively in the adult population after aortic surgery. Conclusions Post-pump chorea and PSP-like syndrome are neurologic complications of major cardiac surgeries that should not be underrecognized. Further reports to establish their common pathogenic mechanism should be encouraged.

A levelized cost of energy (LCOE) is a methodology for comparing power generation costs in the transition to renewable energy (RE). However, the major limitation of evaluating RE based on the LCOE is that it does not consider indirect costs, such as the environmental and curtailment effect. This paper proposes the real LCOE (rLCOE) approach that accounts for indirect and direct generation costs. The mathematical approach to estimating indirect costs is derived from economic theory. The indirect effects, which quantify all benefits generated due to RE, is related to the variability of the share RE in the energy generation mix. The rLCOE enhances the accuracy of the economic comparison of power generation costs and the derivation of the optimal quantities of RE because external effects are incorporated into the LCOE principles. This approach has taken into account electricity demand, fuel prices, and environmental costs for each energy source to adequately compare generation costs. Simulations have been performed to demonstrate the application of the rLCOE approach in the Korean power market. Here, the unit variation of costs with the RE share were analyzed. The results show that indirect cost savings of an additional unit of RE begin to fall in scenario 3 in contrast to the result of LCOE approach indicating higher generation costs with RE share, especially, the proportion of RE in the generation mix is higher than 20%. Thus, the optimal power generation can be evaluated using the rLCOE approach.

Objectives Most previous studies have failed to show a relation between daytime sleepiness and apnoea severity in patients with obstructive sleep apnoea (OSA). We determined the relation between daytime sleepiness and subjective and objective apnoea severity in newly diagnosed patients with moderate-to-severe OSA. Design Retrospective cross-sectional study. Setting Tertiary referral centre. Participants A total of 559 adults with newly diagnosed moderate and severe OSA. Main outcome measures Daytime sleepiness was evaluated using the Epworth Sleepiness Scale (ESS). Subjective and objective apnoea severities were assessed using the Sleep Breathing Scale (SBS) and polysomnography respectively. Sleep quality and depressive symptoms were evaluated using Medical Outcomes Study-Sleep Scale and Beck Depression Inventory (BDI) respectively. Results The mean ESS score was 9.8 (SD 5.0). ESS score was correlated with SBS score (P < 0.001), apnoea−hypopnoea index (AHI) (P = 0.027), minimal oxygen saturation (MinSaO2) (P = 0.021), body mass index (BMI) (P = 0.007) and BDI score (P < 0.001). Linear regression analysis showed that higher SBS (P = 0.005) and BDI scores (P < 0.001) were associated with higher ESS score after controlling for gender, BMI and AHI. Apnoea−hypopnoea index, MinSaO2 and BMI were not independently related to ESS score. Conclusions Daytime sleepiness was related to subjective OSA symptoms but not objective apnoea severity measured by polysomnography in patients with moderate-to-severe OSA. These findings suggest the usefulness of the subjective apnoea severity as an indicator of OSA disease severity.

Background The severity of parkinsonism and response to levodopa vary in patients with multiple system atrophy (MSA) because of the heterogeneity of nigrostriatal neuropathology. Objective To investigate the difference in clinical features between MSA patients with predominantly pre-synaptic nigrostriatal dysfunction and those with trans-synaptic nigrostriatal dysfunction. Methods We retrospectively analyzed clinical data of 61 patients with MSA who underwent both [18F]FP-CIT-PET and [18F]FDG-PET within 3 months of clinical evaluation, and who had ≤3 years of disease duration. Tracer uptake of the striatum on [18F]FP-CIT-PET and glucose metabolism of the striatum on [18F]FDG-PET were analyzed using eight striatal subregional volumes-of-interest templates. The patients were classified into two subgroups according to the predominant pre-synaptic tracer uptake loss of the posterior putamen on [18F]FP-CIT-PET (MSA-SNpc, n = 21) and trans-synaptic dopaminergic dysfunction reflected by both [18F]FP-CIT-PET and [18F]FDG-PET (MSA-STR, n = 40). Results Parkinsonian features were significantly more severe in the MSA-STR group than in the MSA-SNpc group (P = .005) and cerebellar ataxia was significantly more severe in the MSA-SNpc group (P = .036). The cerebellar type of MSA was significantly more common in the MSA-SNpc group (P = .001). There was no difference in age at onset, disease duration at the time of study, or Mini-Mental Status Examination scores between the groups. Conclusions Patients with MSA showed distinct clinical features depending on whether the pattern of nigrostriatal dysfunction was predominantly pre-synaptic or trans-synaptic.

Combined use of 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl)nortropane (FP-CIT) for dopamine transporter imaging and 18F-fludeoxyglucose (FDG) for glucose metabolism shows good diagnostic performance for differential diagnosis of Parkinson disease (PD) and Parkinson plus syndrome (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, and dementia with Lewy bodies). A recent study showed that 18F-FP-CIT positron emission tomography (PET) with early perfusion imaging is useful for the differential diagnosis of PD and Parkinson plus syndrome with lower radiation exposure, time, and cost. In this review, we summarize the advantages of using 18F-FP-CIT PET for perfusion and dopamine transporter imaging, as well as clinical features useful for the differential diagnosis of PD and Parkinson plus syndrome.