Evidence of Inflammation in Parkinson’s Disease and Its Contribution to Synucleinopathy

Accumulation of alpha-synuclein (αSyn) protein in neurons is a renowned pathological hallmark of Parkinson’s disease (PD). In addition, accumulating evidence indicates that activated inflammatory responses are involved in the pathogenesis of PD. Thus, achieving a better understanding of the interaction between inflammation and synucleinopathy in relation to the PD process will facilitate the development of promising disease-modifying therapies. In this review, the evidence of inflammation in PD is discussed, and human, animal, and laboratory studies relevant to the relationship between inflammation and αSyn are explored as well as new therapeutic targets associated with this relationship.

Biomarker in Parkinson’s Disease: Clinical and Biochemical Biomarker

Parkinson’s disease is a neurodegenerative disease compromising progressive motor and non-motor features for a long disease course. Although many drugs controlling parkinsonian symptoms were discovered, treatment with disease-modifying or halting effect was not developed to date. The exploration of reliable biomarkers would be helpful for better predicting disease progression and thereby successful development of disease-modifying therapy. In this review, we will review the clinical biomarkers in the prodromal stage and biomarkers using biological tissue in Parkinson’s disease.

Myotonic dystrophy type 1 with anterior temporal white matter changes mimicking cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

@#Myotonic dystrophy type 1 is the most common type of muscular dystrophy in adults characterized by progressive myopathy, myotonia, and occasional systemic involvement. This is a case of myotonic dystrophy type 1 with cognitive decline showing brain magnetic resonance image abnormality mimicking cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

Validation of the Korean Version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale

Background@#and PurposeImpulse-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 α 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.

Early Impairment of Chopsticks Skills in Parkinsonism Suggests Progressive Supranuclear Palsy

Background@#and PurposeChopsticks are a primary eating utensil in East Asia, but systematic assessments of chopsticks skills in parkinsonian disorders is lacking. We aimed to identify any differences in chopsticks skills in the early stages of Parkinson's disease (PD) and atypical parkinsonism (AP), including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal syndrome (CBS). @*Methods@#We consecutively recruited 111 patients with PD and 74 with AP (40 with PSP, 30 with MSA, and 4 with CBS) who were in a drug-naïve state. The motor and cognitive functions of the patients were evaluated using a standardized protocol. Everyday chopsticks skills were evaluated using a chopsticks questionnaire developed in-house. The chopsticks skills test (CST) involved counting the number of pills that the subject was able to carry using chopsticks between two dishes separated by 20 cm within 20 seconds. @*Results@#Patient responses to the questionnaire indicating poor chopsticks skills (“I cannot pick up some of the food items” or “I cannot use chopsticks anymore”) were present in 23.0% of AP patients and 30% of PSP patients, compared to only 5.6% of PD patients [odd ratio (OR)=5.07 and OR=7.29, p≤0.001 in both]. The performance in the CST was worse in PSP than in PD (p<0.001). The CST results were correlated with hand motor skills including in the coinrotation test, timed figure-tapping test, and motor Unified Parkinson's Disease Rating Scale scores in all of the patient groups (p<0.001). In PSP, a decline in visuospatial function and frontal executive function was associated with a poor performance in the CST in addition to poor motor performance (p<0.05). @*Conclusions@#Impairments in chopsticks skills were more common in PSP than in PD during the early stages of parkinsonism. This suggests that early functional impairment of chopsticks skills can be used as a warning sign for PSP.

Subtypes of Sleep Disturbance in Parkinson's Disease Based on the Cross-Culturally Validated Korean Version of Parkinson's Disease Sleep Scale-2

Trends in the Prevalence of Drug-Induced Parkinsonism in Korea

PURPOSE: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data. MATERIALS AND METHODS: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean National Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed. RESULTS: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p<0.001). Levosulpiride use before and after DIP diagnosis showed a clear trend for decreasing utilization (CAGR: −5.4%, −4.3% respectively), whereas the CAGR for itopride and metoclopramide increased by 12.7% and 6.4%, respectively. In 2015, approximately 46.6% (858/1840 persons) of DIP patients were prescribed offending drugs after DIP diagnosis. The most commonly prescribed causative drug after DIP diagnosis was levosulpiride. CONCLUSION: The prevalence of DIP has increased. To prevent or decrease DIP, we suggest that physicians reduce prescriptions of benzamide derivatives that have been most commonly used, and that attempts be made to find other alternative drugs. Additionally, the need for continuing education about offending drugs should be emphasized.

Validation of the Korean Version of the Scales for Outcomes in Parkinson's Disease-Sleep

BACKGROUND: Sleep problems commonly occur in patients with Parkinson's disease (PD), and are associated with a lower quality of life. The aim of the current study was to translate the English version of the Scales for Outcomes in Parkinson's Disease-Sleep (SCOPA-S) into the Korean version of SCOPA-S (K-SCOPA-S), and to evaluate its reliability and validity for use by Korean-speaking patients with PD. METHODS: In total, 136 patients with PD from 27 movement disorder centres of university-affiliated hospitals in Korea were enrolled in this study. They were assessed using SCOPA, Hoehn and Yahr Scale (HYS), Unified Parkinson's Disease Rating Scale (UPDRS), Parkinson's Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinson's Disease Questionnaire (PDQ39), Neurogenic Orthostatic Hypotension Questionnaire (NOHQ), and Rapid Eye Movement Sleep Behaviour Disorder Questionnaire (RBDQ). The test-retest reliability was assessed over a time interval of 10–14 days. RESULTS: The internal consistency (Cronbach's α-coefficients) of K-SCOPA-S was 0.88 for nighttime sleep (NS) and 0.75 for daytime sleepiness (DS). Test-retest reliability was 0.88 and 0.85 for the NS and DS, respectively. There was a moderate correlation between the NS sub-score and PDSS-2 total score. The NS and DS sub-scores of K-SCOPA-S were correlated with motor scale such as HYS, and non-motor scales such as UPDRS I, UPDRS II, MADS, NMSS, PDQ39, and NOHQ while the DS sub-score was with RBDQ. CONCLUSION: The K-SCOPA-S exhibited good reliability and validity for the assessment of sleep problems in the Korean patients with PD.

Presynaptic Dopaminergic Degeneration in a Patient with Beta-Propeller Protein-Associated Neurodegeneration Documented by Dopamine Transporter Positron Emission Tomography Images: A Case Report

No abstract available.

Patients and Their Caregivers' Burdens for Parkinson's Disease in Korea

OBJECTIVE: Many patients with Parkinson’s disease (PD) suffer from motor and non-motor symptoms. According to these variable symptoms of PD, patients or caregivers have a poorer quality of life than patients with other neurodegenerative diseases. Since the difficulties are varied for all patients, prioritizing their difficulties differs among all cases. The goal of this study was to investigate the burdens of PD among the caregivers as well as patients and to identify areas requiring aid from the government. METHODS: We surveyed the awareness and perceptions of PD in patients and caregivers of PD by a face-to-face questionnaire. The questionnaire was divided into three sections: symptoms of PD (part A), desire for policies (part B), and difficulties faced by their caregivers (part C). Part A comprised 8 questions, Part B had 2 questions, and Part C had 3 questions. RESULTS: In total, 853 subjects (702 patients and 151 caregivers) were enrolled in this study. The major difficulties experienced by PD patients were physical (67%), psychiatric (60%) and socio-economic (52%). Assessing the physical difficulties, more than half the patients experienced severe difficulties (29% very severe, 39% severe). Psychiatric difficulties were assessed as severe (35%) and very severe (21%) among the patients. Severe difficulties were also experienced socio-economically, at 52% in patients and 49% in caregivers, especially among patients in their fifties (58%) and those with their spouse (65%) as caregivers. The topmost need was the introduction of new technology for treatment of PD (62%), followed by relief of costs for treatment (38%) and a family support system (31%). The majority (91%) of the patients were diagnosed with PD within two years after onset of symptoms. CONCLUSION: We know that the difficulties of PD and the needs for government assistance are different between patients and caregivers. These results emphasize that perceiving the difficulties and needs of patients and caregivers early can help to prevent and ameliorate the burden of disease.

Validation of the Korean Version of the Scale for Outcomes in Parkinson's Disease-Autonomic

OBJECTIVE: Autonomic symptoms are commonly observed in patients with Parkinson's disease (PD) and often limit the activities of daily living. The Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) was developed to evaluate and quantify autonomic symptoms in PD. The goal of this study was to translate the original SCOPA-AUT, which was written in English, into Korean and to evaluate its reliability and validity for Korean PD patients. METHODS: For the translation, the following processes were performed: forward translation, backward translation, expert review, pretest of the pre-final version and development of the final Korean version of SCOPA-AUT (K-SCOPA-AUT). In total, 127 patients with PD from 31 movement disorder clinics of university-affiliated hospitals in Korea were enrolled in this study. All patients were assessed using the K-SCOPA-AUT and other motor, non-motor, and quality of life scores. Test-retest reliability for the K-SCOPA-AUT was assessed over a time interval of 10−14 days. RESULTS: The internal consistency and reliability of the K-SCOPA-AUT was 0.727 as measured by the mean Cronbach's α-coefficient. The test-retest correlation reliability was 0.859 by the Guttman split-half coefficient. The total K-SCOPA-AUT score showed a positive correlation with other non-motor symptoms [the Korean version of non-motor symptom scale (K-NMSS)], activities of daily living (Unified Parkinson's Disease Rating Scale part II) and quality of life [the Korean version of Parkinson's Disease Quality of Life 39 (K-PDQ39)]. CONCLUSION: The K-SCOPA-AUT had good reliability and validity for the assessment of autonomic dysfunction in Korean PD patients. Autonomic symptom severities were associated with many other motor and non-motor impairments and influenced quality of life.

Metronidazole-Induced Craniocervical Myoclonus with Reversible Bilateral Dentate Nucleus Lesions

No abstract available.

N30 Somatosensory Evoked Potential Is Negatively Correlated with Motor Function in Parkinson's Disease

OBJECTIVE: The aim of this study was to investigate frontal N30 status in Parkinson's disease (PD) and to examine the correlation between the amplitude of frontal N30 and the severity of motor deficits. METHODS: The frontal N30 was compared between 17 PD patients and 18 healthy volunteers. Correlations between the amplitude of frontal N30 and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score of the more severely affected side was examined. RESULTS: The mean latency of the N30 was not significantly different between patients and healthy volunteers (p = 0.981), but the mean amplitude was lower in PD patients (p < 0.025). There was a significant negative correlation between the amplitude of N30 and the UPDRS motor score (r = -0.715, p = 0.013). CONCLUSIONS: The frontal N30 status indicates the motor severity of PD. It can be a useful biomarker reflecting dopaminergic deficits and an objective measurement for monitoring the clinical severity of PD.

Cognitive Dysfunction in Drug-induced Parkinsonism Caused by Prokinetics and Antiemetics

The use of prokinetics/antiemetics is one of the leading causes of drug-induced parkinsonism (DIP) observed in neurology clinics. Cognitive dysfunction in DIP has recently been recognized, but pathologies related with cognitive dysfunction is unknown. Among our retrospective cohort of 385 consecutive parkinsonian patients enrolled in our parkinsonism registry, 14 patients were identified who satisfied our inclusion criteria: parkinsonism caused by prokinetics/antiemetics, existing T1-weighted 3D volumetric MR images, and normal [18F]-N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane PET scan images. For the comparison of volumetric MR data, 30 age- and sex-matched healthy individuals were included in this study. Among 14 patients with DIP, 4 patients were diagnosed with dementia, and all other patients had mild cognitive impairment (MCI). Comparisons of MR volumetric data between DIP patients with MCI and controls show that cortical gray matter volumes are reduced bilaterally in DIP (P=0.041) without changes in either total white matter volume or total intracranial volume. Among subcortical structures, the volume of the right hippocampus is reduced in DIP patients compared with controls (P=0.011, uncorrected). In DIP, cortical thickness is reduced in the bilateral lingual (P=0.002), right fusiform (P=0.032) and part of the left lateral occipital gyri (P=0.007). Our results suggests that cognitive dysfunction in DIP caused by prokinetics/antiemetics is common. Structural changes in the brain by 3D MRI may be associated with cognitive decline in DIP.

Erratum: Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease

Authors would like to change annotation of variants in Table 1 and its legend according to HGVS nomenclature recommendation.

Utility of the Midbrain Tegmentum Diameter in the Differential Diagnosis of Progressive Supranuclear Palsy from Idiopathic Parkinson's Disease

BACKGROUND AND PURPOSE: Various magnetic resonance (MR) measurements have been proposed to aid in differentiating between progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (IPD); however, these methods have not been compared directly. The aim of this study was to determine which measurement method exhibits the highest power to differentiate between PSP and IPD. METHODS: Brain MR images from 82 IPD and 29 PSP patients were analyzed retrospectively. T1-weighted 3D volumetric axial images, or sagittal images reconstructed from those axial images were examined. MR measurements included the length from the interpeduncular fossa to the center of the cerebral aqueduct at the mid-mammillary-body level, adjusted according to the anterior commissure-posterior commissure length (MB(Tegm)), the ratio of the midbrain area to the pons area (M/P ratio) as measured by both Oba's method (Oba M/P) and Cosottini's method (Cosottini M/P), and a modified MR parkinsonism index (mMRPI). RESULTS: Receiver operating characteristic (ROC) analysis indicated that the areas under the ROC curves (AUCs) exceeded 0.70, with a high intrarater reliability for all MR measurement methods. ROC analyses of four MR measurements yielded AUCs of 0.69-0.76. At the cutoff value with the highest Youden index, mMRPI had the highest sensitivity, while Oba M/P offered the highest specificity. A comparison of the ROC analyses revealed that MB(Tegm) was superior to mMRPI in differentiating PSP from IPD (p=0.049). There was no difference in discriminating power among Oba M/P, Cosottini M/P, and MB(Tegm). CONCLUSIONS: Simple measurements of MB(Tegm) on axial MR images at the mid-mammillary-body level are comparable to measurements of the M/P ratio with regard to their ability to discriminate PSP from IPD.

Myotonic Potentials in the Myopathy Induced by HMG-CoA Reductase Inhibitor

HMG-CoA reductase inhibitor is widely used for the treatment of dyslipidemia, and for the prevention of stroke and cardiovascular disease. However, it is necessary to consider the adverse effects associated with this drug. Myopathy is a well-known side effect of statin therapy, but myotonic potentials in cases with statin myopathy have thus far been reported only rarely. We report four cases of myopathy with myotonic potentials on electromyography after multidrug administration. All of the patients recovered shortly after statin withdrawal.

Analysis of Dosage Mutation in PARK2 among Korean Patients with Early-Onset or Familial Parkinson's Disease

BACKGROUND AND PURPOSE: There is some controversy regarding heterozygous mutations of the gene encoding parkin (PARK2) as risk factors for Parkinson's disease (PD), and all previous studies have been performed in non-Asian populations. Dosage mutation of PARK2, rather than a point mutation or small insertion/deletion mutation, was reported to be a risk factor for familial PD; dosage mutation of PARK2 is common in Asian populations. METHODS: We performed a gene-dosage analysis of PARK2 using real-time polymerase chain reaction for 189 patients with early-onset PD or familial PD, and 191 control individuals. In the case of PD patients with heterozygous gene-dosage mutation, we performed a sequencing analysis to exclude compound heterozygous mutations. The association between heterozygous mutation of PARK2 and PD was tested. RESULTS: We identified 22 PD patients with PARK2 mutations (11.6%). Five patients (2.6%) had compound heterozygous mutations, and 13 patients (6.9%) had a heterozygous mutation. The phase could not be determined in one patient. Three small sequence variations were found in 30 mutated alleles (10.0%). Gene-dosage mutation accounted for 90% of all of the mutations found. The frequency of a heterozygous PARK2 gene-dosage mutation was higher in PD patients than in the controls. CONCLUSIONS: Heterozygous gene-dosage mutation of PARK2 is a genetic risk factor for patients with early-onset or familial PD in Koreans.

Translation and Validation of the Korean Version of the 39-Item Parkinson's Disease Questionnaire

BACKGROUND AND PURPOSE: The importance of health-related quality of life (HrQoL) has been increasingly emphasized when assessing and providing treatment to patients with chronic, progressive, degenerative disorders. The 39-item Parkinson's disease questionnaire (PDQ-39) is the most widely used patient-reporting scale to assess HrQoL in Parkinson's disease (PD). This study evaluated the validity and reliability of the translated Korean version of the PDQ-39 (K-PDQ-39). METHODS: One hundred and two participants with PD from 10 movement disorder clinics at university-affiliated hospitals in South Korea completed the K-PDQ-39. All of the participants were also tested using the Unified Parkinson's Disease Rating Scale (UPDRS), Korean version of the Mini-Mental State Examination (K-MMSE), Korean version of the Montgomery-Asberg Depression Scale (K-MADS), Epworth Sleepiness Scale (ESS) and non-motor symptoms scale (NMSS). Retests of the K-PDQ-39 were performed over time intervals from 10 to 14 days in order to assess test-retest reliability. RESULTS: Each K-PDQ-39 domain showed correlations with the summary index scores (rS=0.559-0.793, p or =0.70). The Guttman split-half coefficient value of the K-PDQ-39 summary index, which is an indicator of test-retest reliability, was 0.919 (p<0.001). All of the clinical variables examined except for age, comprising disease duration, levodopa equivalent dose, modified Hoehn and Yahr stage (H&Y stage), UPDRS part I, II and III, mood status (K-MADS), cognition (K-MMSE), daytime sleepiness (ESS) and (NMSS) showed strong correlations with the K-PDQ-39 summary index (p<0.01). CONCLUSIONS: The K-PDQ-39 has been validated for use in the Korean-speaking PD population. The questionnaire is a valid and reliable assessment tool for assessing the HrQoL of Korean PD patients.

Risk Factors for Peripheral Artery Disease in Patients With Ischemic Stroke or Transient Ischemic Attack

BACKGROUND: Co-morbid vascular disease, such as coronary artery disease or peripheral artery disease (PAD) is frequently combined in patients with ischemic stroke (IS) or transient ischemic attack (TIA). However, PAD has been underestimated and underevaluated in these patients. The aims of this study were to know the prevalence of PAD and to assess the risk factors for PAD in patients with IS or TIA. METHODS: Between February in 2006 and March in 2011, ankle-brachial index (ABI) was measured in 724 patients with acute IS or TIA. We compared the demographics and baseline characteristics, including risk factors and stroke subtypes between patients combined with and without PAD. RESULTS: PAD was found in 13.3% (96/724) and more frequent in patients with large artery disease. Patients with PAD were older (mean age 74.5+/-10.4 vs. 65.5+/-12.5, p<0.001),and had higher body mass index (BMI) (23.15+/-3.46 vs. 24.03+/-3.25; p=0.019), higher serum level of hemoglobin (12.99+/-2.12 vs. 13.68+/-1.87; p=0.001) and severe initial neurological deficit measured by National Institute of Health Stroke Scale (NIHSS) (median 4, IQR:2,7 vs. 2, IQR:1,5; p=0.001) on admission than those without PAD; patients with PAD were more likely to have hypertension (79.2% vs. 61.6%; p=0.001), diabetes (44.8% vs. 29.5%; p=0.004), and previous stroke or TIA (35.4% vs. 23.9%; p=0.022). In multivariable logistic regression analysis, age (OR, 1.069; 95% CI, 1.042-1.096; p<0.001) and diabetes (OR, 1.904; 95% CI, 1.134-3.196; p=0.015) were independently associated with PAD in IS or TIA. CONCLUSIONS: Age and diabetes were independent risk factors for PAD in IS or TIA.