Evaluating the validity and reliability of the Korean version of Scales for Outcomes in Parkinson's Disease-Cognition.

Objective: The Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA-Cog) was developed to screen for cognition in PD. In this study, we aimed to evaluate the validity and reliability of the Korean version of the SCOPA-cog. Methods: We recruited 129 PD patients from 31 clinics with movement disorders in South Korea. The original version of the SCOPA-cognition was translated into Korean using the translation-retranslation method. The test-rest method with an intraclass correlation coefficient (ICC) and Cronbach's alpha coefficient were used to assess reliability. The Spearman's Rank correlation analysis with Montreal Cognitive Assessment-Korean version (MOCA-K) and 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 showed a significant correlation with the K-MMSE and MOCA-K scores (r = 0.546 and r = 0.683, respectively). Conclusions: Our results demonstrate that K-SCOPA-Cog exhibits good reliability and validity.

Opicapone to Treat Early Wearing-off in Parkinson's Disease Patients: The Korean ADOPTION Trial.

BACKGROUND: Increasing levodopa (L-dopa)/dopa decarboxylase inhibitor (DDCI) daily dose or adding a catechol-O-methyltransferase (COMT) inhibitor to levodopa/DDCI therapy are strategies used to manage wearing-off symptoms in Parkinson's disease (PD) patients. OBJECTIVES: To evaluate the COMT inhibitor opicapone versus an additional dose of levodopa to treat early wearing-off in PD patients. METHODS: ADOPTION was a randomized, parallel-group, open-label, Phase 4 study conducted in Korea. At baseline, eligible patients were randomized (1:1) to opicapone 50 mg (n = 87) or L-dopa 100 mg (n = 81) (added to current L-dopa/DDCI therapy) for 4 weeks. The main efficacy endpoint was change from baseline to end of study in absolute off time. Other endpoints included changes in on time, in Movement Disorder Society-Unified Parkinson's Disease Rating Scale and 8-item PD Questionnaire scores, and the Clinical and Patient Global Impression of Improvement/Change. RESULTS: The adjusted mean in absolute off time was significantly greater for opicapone 50 mg than for L-dopa 100 mg (-62.1 vs. -16.7 minutes; P = 0.0015). Opicapone-treated patients also reported a greater reduction in the percentage of off time (P = 0.0015), a greater increase in absolute on time (P = 0.0338) and a greater increase in the percentage of on time (P = 0.0015). There were no significant differences in other secondary endpoints. The L-dopa equivalent daily dose was significantly higher in the opicapone group (750.9 vs. 690.0 mg; P = 0.0247), when a 0.5 conversion factor is applied. CONCLUSIONS: Opicapone 50 mg was more effective than an additional 100 mg L-dopa dose at decreasing off time in patients with PD and early wearing-off.

Caregiver Burden of Patients With Huntington's Disease in South Korea.

OBJECTIVE: This is the first prospective cohort study of Huntington's disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers. METHODS: From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups. RESULTS: Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38-65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson-Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers' demographics, blood relation, and marital and social status did not affect the burden significantly. CONCLUSION: HD patients' neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

Plasma neurofilament light-chain and phosphorylated tau as biomarkers of disease severity in Huntington's disease: Korean cohort data.

OBJECTIVE: To investigate neurofilament light chain (NfL), phosphorylated tau (p-Tau) and total tau (t-Tau) as plasma markers for clinical severity in Korean Huntington's disease (HD) cohort. METHODS: Genetically-confirmed 67 HD patients participated from 13 referral hospitals in South Korea. The subjects were evaluated with the Unified Huntington's Disease Rating Scale (UHDRS), total motor score (TMS) and total functional capacity (TFC), Mini-Mental Status Examination (K-MMSE), Montreal Cognitive Assessment (MoCA-K), and Beck's depression inventory (K-BDI). We measured plasma NfL, p-Tau and t-Tau concentrations using single-molecule array (SIMOA) assays. Stages of HD were classified based on UHDRS-TFC score and plasma markers were analyzed for correlation with clinical severity scales. RESULTS: Plasma NfL was elevated in both 6 premanifest and 61 full manifest HD patients compared to the reference value, which increased further from premanifest to manifest HD groups. The NfL level was not significantly correlated with UHDRS TMS or TFC scores in manifest HD patients. Plasma p-Tau was also elevated in HD patients (p = 0.038). The level was the highest in stage III-V HD (n = 30) group (post-hoc p < 0.05). The p-Tau was correlated with UHDRS TFC scores (adjusted p = 0.002). Plasma t-Tau neither differed among the groups nor associated with any clinical variables. CONCLUSIONS: This study supports plasma NfL being a biomarker for initial HD manifestation in Korean cohort, and a novel suggestion of plasma p-Tau as a potential biomarker reflecting the clinical severity in full-manifest HD.

Diagnostic performance of a high-spatial-resolution voxelwise analysis of neuromelanin-sensitive imaging in early-stage idiopathic Parkinson's disease.

BACKGROUND: Quantitative assessments of neuromelanin (NM) of the substantia nigra pars compacta (SNpc) in neuromelanin-sensitive MRI (NM-MRI) to determine its abnormality have been conducted by measuring either the volume or contrast ratio (CR) of the SNpc. A recent study determined the regions in the SNpc that are significantly different between early-stage idiopathic Parkinson's disease (IPD) patients and healthy controls (HCs) using a high spatial-resolution NM-MRI template, which enables a template-based voxelwise analysis to overcome the susceptibility of CR measurement to inter-rater discrepancy. We aimed to assess the diagnostic performance, which has not been reported, of the CRs between early-stage IPD patients and HCs using a NM-MRI template. METHODS: We retrospectively enrolled early-stage IPD patients (n = 50) and HCs (n = 50) who underwent 0.8-mm isovoxel NM-MRI and dopamine-transporter PET as the standard of reference. A template-based voxelwise analysis revealed two regions in nigrosomes 1 and 2 (N1 and N2, respectively), with significant differences in each substantia nigra (SNpc) between IPD and HCs. The mean CR values of N1, N2, volume-weighted mean of N1 and N2 (N1 + N2), and whole SNpc on each side were compared between IPD and HC using the independent t-test or the Mann-Whitney U test. The diagnostic performance was compared in each region using receiver operating characteristic curves. RESULTS: The mean CR values in the right N1 (0.149459 vs. 0.194505), left N1 (0.133328 vs. 0.169160), right N2 (0.230245 vs. 0.278181), left N2 (0.235784 vs. 0.314169), right N1 + N2 (0.155322 vs. 0.278143), left N1 + N2 (0.140991 vs. 0.276755), right whole SNpc (0.131397 vs. 0.141422), and left whole SNpc (0.127099 vs. 0.137873) significantly differed between IPD patients and HCs (all p < 0.001). The areas under the curve of the left N1 + N2, right N1 + N2, left N1, right N1, left N2, right N2, left whole SNpc, and right whole SNpc were 0.994 (sensitivity, 98.0%; specificity, 94.0%), 0.985, 0.804, 0.802, 0.777, 0.766, 0.632, and 0.606, respectively. CONCLUSION: Our NM-MRI template-based CR measurements revealed significant differences between early-stage IPD patients and HCs. The CR values of the left N1 + N2 demonstrated the highest diagnostic performance.

Nigrosome 1 visibility and its association with nigrostriatal dopaminergic loss in Parkinson's disease.

BACKGROUND: Nigrosome 1 (NG1), a small cluster of dopaminergic cells in the substantia nigra and visible in the susceptibility map-weighted magnetic resonance image (SMwI), is severely affected in Parkinson's disease (PD). However, the degree of nigrostriatal degeneration according to the visibility of NG1 has not yet been well elucidated. METHODS: We consecutively recruited 138 PD and 78 non-neurodegenerative disease (non-ND) patients, who underwent both 18 F-FP-CIT positron emission tomography (PET) and SMwI. Three neurologists and one radiologist evaluated the visibility of NG1 in SMwI. The participants were thereby grouped into visible, intermediate, and non-visible groups. Nigrostriatal dopaminergic input was calculated using the specific binding ratio (SBR) of the 18 F-FP-CIT PET. We determined the threshold of regional SBR for discriminating NG1 visibility and the probability for NG1 visibility according to regional SBR. RESULTS: Visual rating of NG1 showed excellent interobserver agreements as well as high sensitivity and specificity to differentiate the PD group from the non-ND group. NG1 was visible in seven patients (5.1%) in the PD group, who had relatively short disease duration or less severe loss of striatal dopamine. The threshold of putaminal SBR reduction on the more affected side for the disappearance of NG1 was 45.5%, and the probability for NG1 visibility dropped to 50% after the reduction of putaminal SBR to 41% from the normal mean. CONCLUSIONS: Almost half loss of nigrostriatal dopaminergic input is required to dissipate the hyperintensity of NG1 on SMwI, suggesting its utility in diagnosing PD only after the onset of the motor symptoms.

Additional Role of Midbrain F-18 FP-CIT Uptake on PET in Evaluation of Essential Tremor and Parkinsonism.

BACKGROUND: Parkinsonism is a term used for the collection of clinical features that cause movement disorders similar to those in Parkinson's disease. Accurate differentiation of these disorders is critical for the treatment and prognosis of any disease. Fluorine-18 N-(3-fluoropropyl)-2ß- carboxymethoxy-3ß-(4-iodophenyl) nortropane (F-18 FP-CIT) has been used in the evaluation of parkinsonism by its uptake in the dopamine active transporter (DAT) of the striatum. Its uptake in other areas of the brain, such as serotonin transporter (SERT) in the midbrain or thalamus, is also recognised. OBJECTIVE: To investigate whether midbrain SERT uptake of F-18 FP-CIT on positron emission tomography (PET) could be applied to the differentiation of parkinsonism in combination with striatal DAT uptake. METHODS: This retrospective study included clinically diagnosed three essential tremors (ET), 53 parkinsonism patients (21 idiopathic Parkinson's disease (IPD), 6 multiple system atrophy - cerebellar type (MSA-C), 7 multiple system atrophy - parkinsonian type (MSA-P), 8 vascular parkinsonism (VP), and 11 drug-induced parkinsonism (DIP)), and 16 healthy controls. The patient group consisted of 29 men and 27 women (age mean ± SD years, 69.9 ± 8.5 and 69.2 ± 8.9, respectively), and the healthy controls consisted of 8 men and 8 women (age mean ± SD years, 64.5 ± 8.2 and 64.3 ± 7.6, respectively). Mean standardized uptake values (SUVs) and activity volumes were measured from the visualized FP-CIT uptake of the midbrain (substantia nigra and dorsal raphe nucleus) as well as the striatum (caudate nucleus and putamen). The mean SUVs of the occipital region were measured as the background activity. The semiquantitative binding ratio (BR) was calculated using the following formula: BR = (SUVmean of the region of interest - SUVmean of background)/SUVmean of the background. SUV, volume, and BR in each type of parkinsonism were compared with those in healthy controls using both nonparametric and parametric methods. The correlation between the visual score of the qualitative analysis and the BR was examined. RESULTS: Except for the dorsal raphe nucleus in VP, the midbrain BRs in all parkinsonism showed a statistically significant decrease compared to those in healthy controls. Both midbrain and striatal BRs were significantly decreased only in patients with IPD or MSA-P; a greater decrease of substantia nigra BR was identified in MSA-P than in IPD (p < 0.05). The striatal BRs in MSA-C, VP, and DIP showed no significant difference from those in healthy controls. Finally, four patterns of uptake were identified: 1) decreased striatal and midbrain uptake for IPD and MSA-P, 2) normal striatal uptake and decreased midbrain uptake (both substantia nigra and dorsal raphe nucleus) for MSA-C and DIP, 3) normal striatal uptake and decreased substantia nigra uptake (without decreased dorsal raphe nucleus uptake) for VP, and 4) normal striatal and midbrain uptake for ET. CONCLUSION: The possible differential diagnoses were split into two groups when only striatal uptake was considered but they were divided into four groups after adding midbrain uptake. Although additional midbrain F-18 FP-CIT uptake still could not make a final definitive diagnosis, it could provide another piece of information and specific diagnostic guidelines for the differentiation of parkinsonism.

Correlation Between Neuromelanin-Sensitive MRI and 18F-FP-CIT PET in Early-Stage Parkinson's Disease: Utility of a Voxel-Wise Analysis by Using High-Spatial-Resolution MRI.

BACKGROUND AND PURPOSE: The correlation between dopamine transporter (DAT) imaging and neuromelanin-sensitive magnetic resonance imaging (NM-MRI) in early-stage Parkinson's disease (PD) has not yet been established. This study aimed to determine the correlation between NM-MRI and DAT positron-emission tomography (PET) in patients with early-stage PD. METHODS: Fifty drug-naïve patients with early-stage PD who underwent both 0.8-mm isovoxel NM-MRI and DAT PET were enrolled retrospectively. Using four regions of interest (nigrosome 1 and nigrosome 2 [N1 and N2] regions) from a previous study, the contrast ratios (CRs) of 12 regions were measured: N1, N2, flipped N1, flipped N2, combined N1 and N2, and whole substantia nigra pars compacta [SNpc] (all on both sides). The clinically more affected side was separately assessed. The standardized uptake value ratios (SUVRs) were measured in the striatum using DAT PET. A partial correlation analysis was performed between the SUVR and CR measurements. RESULTS: CR of the flipped left N1 region was significantly correlated with SUVR of the right posterior putamen (p=0.047), and CR values of the left N1 region, left N2 region, flipped right N1 region, and combined left N1 and N2 regions were significantly correlated with SUVR of the left posterior putamen (p=0.011, 0.038, 0.020, and 0.010, respectively). SUVR of the left anterior putamen was significantly correlated with CR of the left N2 region (p=0.027). On the clinically more affected side, the CR values of the N1 region, combined N1 and N2 regions, and the whole SNpc were significantly correlated with SUVR of the posterior putamen (p=0.001, 0.024, and 0.021, respectively). There were significant correlations between the SUVR of the anterior putamen and the CR values of the N1 region, combined N1 and N2 regions, and whole SNpc (p=0.027, 0.001, and 0.036, respectively). CONCLUSIONS: This study found that there were significant correlations between CR values in the SNpc on NM-MRI and striatal SUVR values on DAT PET on both sides in early-stage PD.

Movement Disorders Associated With Cerebral Artery Stenosis: A Nationwide Study.

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.

Pain in atypical parkinsonism, vascular parkinsonism, and Parkinson's disease.

BACKGROUND: Pain is a common symptom in Parkinson's disease (PD) and is considered a pre-motor symptom suggesting sensory involvement in the pre-motor stage. Pain in other parkinsonian disorders such as atypical parkinsonism and vascular parkinsonism (VP) has been investigated in only a few studies. The characteristics of pain in other parkinsonian disorders, including the temporal relationships between pain and motor symptoms, were investigated in the present study. METHODS: A total of 236 PD, 42 multiple system atrophy (MSA), 31 progressive supranuclear palsy (PSP), and 38 VP patients were screened for pain. After excluding patients with dementia and pain not related to PD, the presence of pain, severity, onset, type, and location were compared among the four patient groups. RESULTS: Difference was not observed in pain presence (χ2 = 3, p = 0.186), severity (F = 1.534, p = 0.207), or type (χ2 = 6, p = 0.400) among the four groups. However, the temporal relationship between pain and motor symptoms differed (H(3) = 8.764, p = 0.033). Pain predated motor symptoms in PD, MSA, and VP but often followed motor symptoms in PSP. The pain location in the body was different among the four patient groups (χ2 = 21, p = 0.018), and leg involvement was more common in PSP. CONCLUSION: The present study results suggest that pain can be a pre-motor symptom in PD, MSA, and VP but not in PSP, implying different pain pathogeneses in these disorders. Pain locations were other for each group, which requires further investigation with a more extensive study cohort.

A prospective multi-centre study of susceptibility map-weighted MRI for the diagnosis of neurodegenerative parkinsonism.

OBJECTIVES: This study aimed to compare susceptibility map-weighted imaging (SMwI) using various MRI machines (three vendors) with N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophe nyl)nortropane (18F-FP-CIT) PET in the diagnosis of neurodegenerative parkinsonism in a multi-centre setting. METHODS: We prospectively recruited 257 subjects, including 157 patients with neurodegenerative parkinsonism, 54 patients with non-neurodegenerative parkinsonism, and 46 healthy subjects from 10 hospitals between November 2019 and October 2020. All participants underwent both SMwI and 18F-FP-CIT PET. SMwI was interpreted by two independent reviewers for the presence or absence of abnormalities in nigrosome 1, and discrepancies were resolved by consensus. 18F-FP-CIT PET was used as the reference standard. Inter-observer agreement was tested using Cohen's kappa coefficient. McNemar's test was used to test the agreement between the interpretations of SMwI and 18F-FP-CIT PET per participant and substantia nigra (SN). RESULTS: The inter-observer agreement was 0.924 and 0.942 per SN and participant, respectively. The diagnostic sensitivity of SMwI was 97.9% and 99.4% per SN and participant, respectively; its specificity was 95.9% and 95.2%, respectively, and its accuracy was 97.1% and 97.7%, respectively. There was no significant difference between the results of SMwI and 18F-FP-CIT PET (p > 0.05, for both SN and participant). CONCLUSIONS: This study demonstrated that the high diagnostic performance of SMwI was maintained in a multi-centre setting with various MRI scanners, suggesting the generalisability of SMwI for determining nigrostriatal degeneration in patients with parkinsonism. KEY POINTS: • Susceptibility map-weighted imaging helps clinicians to predict nigrostriatal degeneration. • The protocol for susceptibility map-weighted imaging can be standardised across MRI vendors. • Susceptibility map-weighted imaging showed diagnostic performance comparable to that of dopamine transporter PET in a multi-centre setting with various MRI scanners.

Automated assessment of the substantia nigra on susceptibility map-weighted imaging using deep convolutional neural networks for diagnosis of Idiopathic Parkinson's disease.

OBJECTIVES: Despite its use in determining nigrostriatal degeneration, the lack of a consistent interpretation of nigrosome 1 susceptibility map-weighted imaging (SMwI) limits its generalized applicability. To implement and evaluate a diagnostic algorithm based on convolutional neural networks for interpreting nigrosome 1 SMwI for determining nigrostriatal degeneration in idiopathic Parkinson's disease (IPD). METHODS: In this retrospective study, we enrolled 267 IPD patients and 160 control subjects (125 patients with drug-induced parkinsonism and 35 healthy subjects) at our institute, and 24 IPD patients and 27 control subjects at three other institutes on approval of the local institutional review boards. Dopamine transporter imaging served as the reference standard for the presence or absence of abnormalities of nigrosome 1 on SMwI. Diagnostic performance was compared between visual assessment by an experienced neuroradiologist and the developed deep learning-based diagnostic algorithm in both internal and external datasets using a bootstrapping method with 10000 re-samples by the "pROC" package of R (version 1.16.2). RESULTS: The area under the receiver operating characteristics curve (AUC) (95% confidence interval [CI]) per participant by the bootstrap method was not significantly different between visual assessment and the deep learning-based algorithm (internal validation, .9622 [0.8912-1.0000] versus 0.9534 [0.8779-0.9956], P = .1511; external validation, 0.9367 [0.8843-0.9802] versus 0.9208 [0.8634-0.9693], P = .6267), indicative of a comparable performance to visual assessment. CONCLUSIONS: Our deep learning-based algorithm for assessing abnormalities of nigrosome 1 on SMwI was found to have a comparable performance to that of an experienced neuroradiologist.

Early-stage Parkinson's disease: Abnormal nigrosome 1 and 2 revealed by a voxelwise analysis of neuromelanin-sensitive MRI.

Previous pathologic studies evaluated the substantia nigra pars compacta (SNpc) of a limited number of idiopathic Parkinson's disease (IPD) patients with relatively longer disease durations. Therefore, it remains unknown which region of the SNpc is most significantly affected in early-stage IPD. We hypothesized that a voxelwise analysis of thin-section neuromelanin-sensitive MRI (NM-MRI) may help determine the significantly affected regions of the SNpc in early-stage IPD and localize these areas in each nigrosome on high-spatial-resolution susceptibility map-weighted imaging (SMwI). Ninety-six healthy subjects and 50 early-stage IPD patients underwent both a 0.8 × 0.8 × 0.8 mm3 NM-MRI and a 0.5 × 0.5 × 1.0 mm3 multi-echo gradient-recalled echo imaging for SMwI. Both NM-MRI and SMwI templates were created by using image data from the 96 healthy subjects. Permutation-based nonparametric tests were conducted to investigate spatial differences between the two groups in NM-MRI, and the results were displayed on both NM-MRI and SMwI templates. The posterolateral and anteromedial regions of the SNpc in NM-MRI were significantly different between the two groups, corresponding to the nigrosome 1 and nigrosome 2 regions, respectively, on the SMwI template. There were the areas of significant spatial difference in the hypointense SN on SMwI between early-stage IPD patients and healthy subjects. These areas on SMwI were slightly greater than those on NM-MRI, including the areas showing group difference on NM-MRI. Our voxelwise analysis of NM-MRI suggests that two regions (nigrosome 1 and nigrosome 2) of the SNpc are separately affected in early-stage IPD.

Cortical thinning pattern according to differential nigrosome involvement in patients with Parkinson's disease.

The pathological hallmark of Parkinson's disease (PD) is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, where the dopaminergic neurons form five clusters called nigrosomes 1-5 (N1-N5). N1 is the largest and considered to be the most affected by PD, followed by N2, N4, N3, and N5. Recently, an MRI study suggested a sequential progression of loss from N1 to N4. As the extent of cortical thinning widens as PD progresses, we aimed to define cortical thinning patterns according to the differential involvement of N1 and N4 in PD patients. Cortical thickness was analyzed in 83 PD patients (29 with N1 loss on at least one side of the brain, but no N4 loss; and 54 with N4 loss on at least one side) and 35 healthy subjects with age, sex, disease duration, and intracranial volume as covariates. On patient-wise analysis, for areas with more cortical thinning than the controls, PD patients with N4 loss had wider cortical thinning involving more dorsolateral prefrontal cortex and temporal areas than PD patients with only N1 loss, but cortical thinning did not significantly differ between these two patient groups. However, cortical thinning was more apparent in hemisphere-level analysis with statistically significant clusters being found more in hemispheres with N4 loss than hemispheres with N1 loss in PD patients compared to normal hemispheres of the controls. Cortical thinning occurred in a similar propagation pattern to that seen with PD progression, supporting past hypotheses on the sequential progression of nigrosome loss from N1 to N4.

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

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 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.

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

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 α 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.

Factors influencing self-management in Parkinson's disease: A cross-sectional study.

This study aimed to identify factors influencing self-management in patients with Parkinson's disease (PD) based on social cognitive theory. A cross-sectional design was used; data were collected at three tertiary medical centers in Korea from a convenience sample of 356 PD patients. Higher self-management scores were associated with higher education level, having a religion, and higher family income. Self-management score was positively correlated with activities of daily living, self-efficacy, and social support, and negatively correlated with non-motor symptoms. Hierarchical regression analysis revealed that demographic factors and non-motor symptoms explained 26.2% of the variance in self-management in PD. The explanatory power increased by 7.5% when self-efficacy was added, and by 6.7% when social support was added. Assessment of self-management in patients with PD should consider self-efficacy and social support, along with demographic factors and non-motor symptoms. Self-management programs that reflect these factors may be useful for improving self-management in PD patients.

Nigrosome 1 imaging: technical considerations and clinical applications.

A pathological study by Damier et al demonstrated that nigrosome 1, a dopaminergic neuron-rich region in the substantial nigra, is the most severely affected region in idiopathic Parkinson's disease. Since then, researchers have identified the location of nigrosome 1 in the dorsal aspect of the substantia nigra using susceptibility-weighted imaging in MRI. Although this observation was reconfirmed by various imaging techniques and imaging planes, non-standardized imaging methods may rather limit the generalized use of this imaging finding. The aim of this review is to revisit the anatomical definition of the nigrosome 1 region using high-spatial-resolution susceptibility map-weighted MRI in order to help the readers to determine the presence or absence of an abnormality in the nigrosome 1 region. Thereafter, we discuss the current status of nigrosome 1 imaging at 3 T and show how to improve the imaging quality for better assessment of nigrosome 1. We also illustrate the imaging findings of various patients who presented with parkinsonism, which can help the readers to learn how to use these images in practice. Lastly, we discuss potential future works with nigrosome 1 susceptibility map-weighted MRI.

Initial diagnostic workup of parkinsonism: Dopamine transporter positron emission tomography versus susceptibility map-weighted imaging at 3T.

BACKGROUND AND PURPOSE: Evaluation of dorsal nigral hyperintensity on MRI can help detect nigrostriatal degeneration. We aimed to compare the diagnostic performance between susceptibility map-weighted imaging (SMWI) and N-3-fluoropropyl-2-ß-carbomethoxy-3-ß-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET) as an initial diagnostic tool of parkinsonism. MATERIALS AND METHODS: This local ethics committee-approved retrospective study enrolled 223 patients with parkinsonism and 15 healthy subjects (mean age, 69.7 years; 135 females) who underwent both SMWI at 3T and 18F-FP-CIT PET. The diagnostic performances of the two tests for nigrostriatal degeneration were compared by evaluating whether the 90% confidence interval (CI) of the difference between the two tests was within the equivalence margin by using the DTComPair package of R. The concordance rate was tested by Cohen's kappa. RESULTS: The diagnostic sensitivities of SMWI and 18F-FP-CIT PET were 94.5% and 100% per SN and 100% and 100% per participant, respectively; their specificities were 95.3% and 86.7% per SN and 94.4% and 84.0% per participant, respectively. While the diagnostic sensitivity was comparable between the two tests for each SN and participant, the lower 90% CI of the differences in the specificity were -0.086 per SN and -0.104 per participant, indicating a higher diagnostic specificity of SMWI than that of 18F-FP-CIT PET. When excluding 20 participants with basal ganglia lesions, the two tests exhibited similar diagnostic performance and had excellent agreement (k = 0.899 per SN; k = 0.945 per participant). CONCLUSION: For patients with parkinsonism, SMWI and 18F-FP-CIT PET exhibit similar diagnostic performance.