Hyeo Il Ma

Association of mutations in the glucocerebrosidase gene with Parkinson disease in a Korean population

Recent studies have shown an association between Parkinson disease (PD) and mutations in the gene encoding the lysosomal enzyme glucocerebrosidase (GBA), which is deficient in patients with Gaucher disease. In Asian populations, 2 mutational analysis studies have been performed in all exons of GBA; one study in a Japanese population showed the highest odds ratio among all ethnic groups, whereas the other study in ethnic Chinese observed a trend of a higher frequency of GBA mutation in PD patients without statistical significance. To investigate whether there is an association between PD and mutations of GBA in a Korean population, we analyzed mutations of GBA and compared mutation frequencies between Korean PD patients and a control population. We analyzed mutations in GBA by sequencing exons of GBA in 277 Korean PD patients and 291 control subjects. All exons of GBA were sequenced in all PD cases and 100 control subjects. Exon 2 and exons 5-11, where mutations of GBA were found in our PD patients, were analyzed in an additional 191 control subjects. Five different pathogenic heterozygous GBA mutations, including N188S, P201H, R257Q, S271G, and L444P, were identified in 9 PD cases (3.2%), whereas there were no GBA mutations found in control subjects (p<0.01, OR 20.6, 95% CI 1.2-356.4). The mean age-at-onset of heterozygous GBA variants carriers was younger than that of non-carriers (48.6±11.9 versus 57.9±13.5, p<0.05, Mann-Whitney test). Our results suggest that heterozygous mutations of GBA represent a risk factor for PD in Koreans.

Validation of the Korean-Version of the Nonmotor Symptoms Scale for Parkinson's Disease

Background and Purpose Non-motor symptoms are common in Parkinsons disease (PD), and are the primary cause of disability in many PD patients. Our aim in this study was to translate the origin non-motor symptoms scale for PD (NMSS), which was written in English, into Korean (K-NMSS), and to evaluate its reliability and validity for use with Korean-speaking patients with PD. Methods In total, 102 patients with PD from 9 movement disorders sections of university teaching hospitals in Korea were enrolled in this study. They were assessed using the K-NMSS, the Unified Parkinsons Disease Rating Scale (UPDRS), the Korean version of the Mini-Mental Status Examination (K-MMSE), the Korean version of the Montgomery-Asberg Depression Rating Scale (K-MADS), the Epworth Sleepiness Scale (ESS), and Parkinsons Disease Questionnaire 39 (PDQ39). Test-retest reliability was assessed over a time interval of 10-14 days in all but one patient. Results The K-NMSS was administered to 102 patients with PD. The internal consistency and reliability of this tool was 0.742 (mean Cronbachs α-coefficient). The test-retest correlation reliability was 0.941 (Guttman split-half coefficient). There was a moderate correlation between the total K-NMSS score and the scores for UPDRS part I [Spearmans rank correlation coefficient, (rS)=0.521, p<0.001] and UPDRS part II (rS=0.464, p=0.001), but there was only a weak correlation between the total K-NMSS score and the UPDRS part III score (rS=0.288, p=0.003). The total K-NMSS score was significantly correlated with the K-MADS (rS=0.594, p<0.001), K-MMSE (rS=-0.291, p=0.003), and ESS (rS=0.348, p<0.001). The total K-NMSS score was also significantly and positively correlated with the PDQ39 score (rS=0.814, p<0.001). Conclusions The K-NMSS exhibited good reliability and validity for the assessment of non-motor symptoms in Korean PD patients.

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 Parkinsons disease questionnaire (PDQ-39) is the most widely used patient-reporting scale to assess HrQoL in Parkinsons 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 Parkinsons 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<0.001). Six out of eight domains met the acceptable standard of reliability (Cronbachs α coefficient ≥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.

Dura Mater Graft-Associated Creutzfeldt-Jakob Disease: The First Case in Korea

Since 1987, dura mater graft-associated iatrogenic Creutzfeldt-Jakob disease (dCJD) has been reported in many countries. We report the first case of dCJD in Korea. A 54-yr-old woman, who underwent resection of the meningioma in the left frontal region and received a dura mater graft 23 yr ago presented with dysesthesia followed by psychiatric symptoms and ataxia. Her neurological symptoms rapidly progressed to such an extent that she exhibited myoclonus, dementia, and pyramidal and extrapyramidal signs within 8 weeks. The 14-3-3 protein was detected in her cerebrospinal fluid; however, an electroencephalogram did not reveal characteristic positive sharp wave complexes. Diffusion-weighted magnetic resonance images, obtained serially over 64 days, revealed the rapid progression of areas of high signal intensity in the caudate nucleus and cingulate gyrus to widespread areas of high signal intensity in the cortex and basal ganglia. Pathological examination of brain biopsy specimens confirmed the presence of spongiform changes and deposition of prion protein in the neurons and neuropils.

Correlating Parkinson’s disease motor symptoms with three-dimensional [18F]FP-CIT PET

PurposeTo investigate the correlation between the striatal three-dimensional location and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score in the context of idiopathic Parkinson’s disease (PD) through radiolabeled N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane positron emission tomography/computed tomography (FP-CIT PET/CT).Materials and methodsIn this cross-sectional study, we assessed the UPDRS motor score and performed FP-CIT PET/CT in patients with PD. Thirty-eight patients with idiopathic PD [average 70xa0years of age (range 49–86); male:female ratio 12:26] were enrolled. The correlation between FP-CIT PET/CT and the UPDRS III scores was investigated after the transformation of PET images by an alternative method using MATLAB.ResultsLeft caudate nucleus uptake negatively correlated with UPDRS items 18, 20 (face), 22 (right arm and leg), 23, 24 (right side), 26 (right side), 27, 30, and 31, while right caudate nucleus uptake positively correlated with items 18, 22 (left arm), 26, and 29. Putamen uptake correlated with items 22 and 25. Left caudate nucleus uptake positively correlated with axial and akinetic-rigidity symptoms.ConclusionsFP-CIT uptake in specific basal ganglia structures strongly correlated with the UPDRS III motor score. Among these, the left caudate nucleus exhibited the strongest relationship with axial and akinetic-rigidity PD symptoms.

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. Methodsn 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. Resultsn 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)]. Conclusionn 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.

Lack of association between LRRK2 G2385R and cognitive dysfunction in Korean patients with Parkinson’s disease

Aside from the glucocerebrosidase gene, the genetic risk factors for cognitive decline in Parkinsons disease (PD) are controversial. We investigated whether the G2385R polymorphism in leucine-rich repeat kinase 2 gene (LRRK2), a risk variant for the development of PD in East Asians, is associated with cognitive dysfunction in PD. We recruited 299 PD patients, consisting of 23 carriers and 276 non-carriers of LRRK2 G2385R, from 14 centers. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) or the Montreal Cognitive Assessment (MoCA). PD with cognitive dysfunction was defined as an MMSE Z score that, adjusting for age at study entry and years of education, was below -1.0 standard deviations. In multivariate analysis, PD duration, age at study entry and depression were significant risk factors for cognitive dysfunction as assessed by MMSE performance or the MoCA. In linear regression analysis of the association between MMSE Z scores and PD duration, there was no significant difference associated with the LRRK2 G2385R genotype. The interaction terms between PD duration and the LRRK2 G2385R genotype were not significant for the MMSE Z score but were significant for the MoCA. In conclusion, the LRRK2 G2385R genotype may not be associated with cognitive dysfunction in PD.

Parkinson’s disease might increase the risk of cerebral ischemic lesions

Background: Parkinsons disease (PD) is the second most common neurodegenerative disease in the elderly. Cerebrovascular diseases such as cerebral ischemic lesion (CIL) also commonly occur in elderly adults. However, previous studies on the relationship between PD and cerebrovascular disease have not found consistent results. Therefore, we conducted this study to evaluate whether or not PD is related to an increased prevalence of ischemic cerebrovascular lesions. Methods: This study recruited 241 patients with PD and 112 healthy controls (HCs). All subjects underwent brain magnetic resonance imaging and general neuropsychological tests. The motor severity of PD was evaluated according to the Hoehn and Yahr stage (HY stage), and the severity of CIL in all subjects was classified according to Fazekas grade. The PD patients were classified into two subgroups according to HY stage (Group 1 - HY 1, 2; Group 2 - HY 3 to 5). Results: Among all PD patients, 76% had small vessel disease, while 44% of all HCs had small vessel disease (p<0.001). Regarding the difference between the two subgroups according to motor severity, group 2 showed significantly higher Fazekas scale score and more severe CIL, indicating a higher prevalence of small vessel disease compared to group 1. Conclusion: This study demonstrates that PD patients have a significantly higher prevalence of CIL compared to HCs. Therefore, although the present study is not a large-scale study, we cautiously suggest that PD can play an important role as a risk factor in the occurrence of ischemic cerebrovascular disease.

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

Background Sleep problems commonly occur in patients with Parkinsons 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 Parkinsons 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 Parkinsons Disease Rating Scale (UPDRS), Parkinsons Disease Sleep Scale 2nd version (PDSS-2), Non-motor Symptoms Scale (NMSS), Montgomery Asberg Depression Scale (MADS), 39-item Parkinsons 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 (Cronbachs 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.