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Introduction: Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a powerful early predictor of dementia with Lewy bodies (DLB) and Parkinson's disease (PD). This provides an opportunity to directly observe the evolution of prodromal DLB and to identify which cognitive variables are the strongest predictors of evolving dementia., Methods: IRBD participants (n = 754) from 10 centers of the International RBD Study Group underwent annual neuropsychological assessment. Competing risk regression analysis determined optimal predictors of dementia. Linear mixed-effect models determined the annual progression of neuropsychological testing., Results: Reduced attention and executive function, particularly performance on the Trail Making Test Part B, were the strongest identifiers of early DLB. In phenoconverters, the onset of cognitive decline began up to 10 years prior to phenoconversion. Changes in verbal memory best differentiated between DLB and PD subtypes., Discussion: In iRBD, attention and executive dysfunction strongly predict dementia and begin declining several years prior to phenoconversion., Highlights: Cognitive decline in iRBD begins up to 10 years prior to phenoconversion. Attention and executive dysfunction are the strongest predictors of dementia in iRBD. Decline in episodic memory best distinguished dementia-first from parkinsonism-first phenoconversion., (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Evaluating eye movements in Parkinson's disease (PD) provides valuable insights into the underlying pathophysiological changes., Objective: The aim was to investigate the relationship between monoaminergic degeneration and ocular motor abnormalities in de novo PD., Methods: Drug-naive PD patients who underwent N-(3-[ 18 F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane positron emission tomography scans and video-oculography at diagnosis were eligible. Measurements of saccadic accuracy, latency, and smooth pursuit gain and square wave jerk frequency were collected. Patients underwent Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and detailed cognitive tests. We investigated the associations between ocular motor measurements and specific tracer uptake ratios (SUR) in the caudate nucleus, anterior and posterior putamen, thalamus, and dorsal raphe nuclei, along with motor and cognitive symptoms., Results: One-hundred twenty-four subjects were included in this study. Saccadic accuracy was positively associated with parkinsonian motor severity expressed as Hoehn and Yahr stages, MDS-UPDRS Part III scores, and subscores for bradykinesia and rigidity but not with tremor scores (P FDR  < 0.05). Saccadic accuracy correlated with poor performances in the Rey-Complex-Figure copy, and latency with the Digit Symbol Coding and the Montreal Cognitive Assessment scores (P FDR  < 0.05). Prolonged saccadic latency correlated with reduced thalamic SUR, whereas decreased saccadic accuracy correlated with reduced SUR in the anterior and posterior putamen (P FDR  < 0.05). Reduced smooth pursuit gain showed associations with reduced SUR in the dorsal raphe, a serotonin-predominant region, but did not correlate with parkinsonism severity scores., Conclusion: Defective dopaminergic and nondopaminergic neural systems may discretely influence ocular motor function in de novo PD patients. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background: A brain glucose metabolism pattern related to phenoconversion in patients with idiopathic/isolated REM sleep behaviour disorder (iRBDconvRP) was recently identified. However, the validation of the iRBDconvRP in an external, independent group of iRBD patients is needed to verify the reproducibility of such pattern, so to increase its importance in clinical and research settings. The aim of this work was to validate the iRBDconvRP in an independent group of iRBD patients., Methods: Forty iRBD patients (70 ± 5.59 years, 19 females) underwent brain [ 18 F]FDG-PET in Seoul National University. Thirteen patients phenoconverted at follow-up (7 Parkinson disease, 5 Dementia with Lewy bodies, 1 Multiple system atrophy; follow-up time 35 ± 20.56 months) and 27 patients were still free from parkinsonism/dementia after 62 ± 29.49 months from baseline. We applied the previously identified iRBDconvRP to validate its phenoconversion prediction power., Results: The iRBDconvRP significantly discriminated converters from non-converters iRBD patients (p = 0.016; Area under the Curve 0.74, Sensitivity 0.69, Specificity 0.78), and it significantly predicted phenoconversion (Hazard ratio 4.26, C.I.95%: 1.18-15.39)., Conclusions: The iRBDconvRP confirmed its robustness in predicting phenoconversion in an independent group of iRBD patients, suggesting its potential role as a stratification biomarker for disease-modifying trials., (© 2023. The Author(s).)

Background: The isolated rapid-eye-movement sleep behavior disorder (iRBD) is a prodromal condition of Lewy body disease including Parkinson's disease and dementia with Lewy bodies (DLB). We aim to investigate the longitudinal evolution of DLB-related cortical thickness signature in a prospective iRBD cohort and evaluate the possible predictive value of the cortical signature index in predicting dementia-first phenoconversion in individuals with iRBD., Methods: We enrolled 22 DLB patients, 44 healthy controls, and 50 video polysomnography-proven iRBD patients. Participants underwent 3-T magnetic resonance imaging (MRI) and clinical/neuropsychological evaluations. We characterized DLB-related whole-brain cortical thickness spatial covariance pattern (DLB-pattern) using scaled subprofile model of principal components analysis that best differentiated DLB patients from age-matched controls. We analyzed clinical and neuropsychological correlates of the DLB-pattern expression scores and the mean values of the whole-brain cortical thickness in DLB and iRBD patients. With repeated MRI data during the follow-up in our prospective iRBD cohort, we investigated the longitudinal evolution of the cortical thickness signature toward Lewy body dementia. Finally, we analyzed the potential predictive value of cortical thickness signature as a biomarker of phenoconversion in iRBD cohort., Results: The DLB-pattern was characterized by thinning of the temporal, orbitofrontal, and insular cortices and relative preservation of the precentral and inferior parietal cortices. The DLB-pattern expression scores correlated with attentional and frontal executive dysfunction (Trail Making Test-A and B: R = - 0.55, P = 0.024 and R = - 0.56, P = 0.036, respectively) as well as visuospatial impairment (Rey-figure copy test: R = - 0.54, P = 0.0047). The longitudinal trajectory of DLB-pattern revealed an increasing pattern above the cut-off in the dementia-first phenoconverters (Pearson's correlation, R = 0.74, P = 6.8 × 10 -4 ) but no significant change in parkinsonism-first phenoconverters (R = 0.0063, P = 0.98). The mean value of the whole-brain cortical thickness predicted phenoconversion in iRBD patients with hazard ratio of 9.33 [1.16-74.12]. The increase in DLB-pattern expression score discriminated dementia-first from parkinsonism-first phenoconversions with 88.2% accuracy., Conclusion: Cortical thickness signature can effectively reflect the longitudinal evolution of Lewy body dementia in the iRBD population. Replication studies would further validate the utility of this imaging marker in iRBD., (© 2023. The Author(s).)

Background: Recent studies suggest that GTP cyclohydrolase 1 (GCH-1) variant may be a risk factor for nigral degeneration causing PD., Methods: A 49-year-old Korean woman visited our movement disorder clinic with the initial presentation of Parkinsonism starting at age 47. We monitored the degree of nigral degeneration with serial FP-CIT PET throughout the course of her disease (2, 8 and 11 years from disease onset)., Results: The initial clinical presentation was consistent with intrinsic dopamine deficiency caused by GCH-1 variant. However, her follow-up disease course was consistent with Parkinsonism caused by nigral neurodegeneration. We found a novel GCH-1 variant in the current case. The disease course of the patient was overall benign in motor and non-motor aspects, corresponding to previously reported GCH-1 cases with PD. Serial FP-CIT PET scans showed normal initial FP-CIT binding followed by a continuous decline of the putaminal binding ratio. However, the decreased binding ratio could not sufficiently explain the corresponding clinical duration of the patient. Therefore, dopamine deficiency by GCH-1 genetic variant contributed to Parkinsonism in the current case with subclinical nigral degeneration., Conclusion: Our case suggests that GCH-1 variant causes Parkinsonism by unmasking the subclinical nigral pathology, not by causing the nigral neurodegeneration.

Introduction: Dopa-responsive dystonia (DRD) related to GCH1 mutation is a biochemical disorder. DRD is majorly characterized by dystonia and/or parkinsonism. Although clinical disorders show a dramatic positive response to levodopa, there are controversies over the residual signs following treatment. This study was designed to investigate the residual signs following levodopa treatment in Korean DRD patients with GCH1 mutation., Methods: A structured questionnaire was prepared to obtain information about demographic factors, clinical characteristics, genetic data, neuroimaging data and residual signs following levodopa treatment of the patients, and was sent to movement specialists at tertiary hospitals. The data collected from the returned forms were analyzed using appropriate statistical methods such as Student's t-test, Mann-Whitney U test, Chi-square test or Fisher's exact test., Results: Thirty-nine DRD Korean patients with GCH1 mutation were recruited. One patient was presented with only parkinsonism. Dystonia was completely resolved in 32 out of 38 patients following treatment, while parkinsonism improved without residual signs in 8 out of 9 patients. The frequency of the residual signs in Korean patients (15.8% for dystonia and 11.1% for parkinsonism) is similar to that observed in Chinese patients, but lower in Western patients. Furthermore, these signs were more frequent in those patients with a delay in their diagnosis, and those who were relatively older at the time of diagnosis., Conclusions: Ethnic differences, age at diagnosis, and a temporal gap between the onset and diagnosis in Korean patients may influence the remaining neurologic abnormalities of DRD., (Copyright © 2019. Published by Elsevier Ltd.)

Objective: Rapid eye movement sleep behavior disorder (RBD) is a common sleep disturbance in patients with neurodegenerative disorders. We aimed to compare sleep parameters among the different types of RBD patients., Methods: A total of 122 patients with dream enactment behavior were screened. Of these, 92 patients who were diagnosed with RBD by polysomnography were included in this study. Enrolled patients with RBD were classified into four groups based on the following diagnoses: idiopathic RBD (iRBD); RBD with Parkinson disease (PD-RBD); multiple system atrophy (MSA) with RBD (MSA-RBD); and dementia with Lewy bodies (DLB) with RBD (DLB-RBD). Various clinical and polysomnographic parameters were compared., Results: Among the 92 patients with RBD, 35 had iRBD, 25 had PD-RBD, 17 had MSA-RBD, and 15 had DLB-RBD. The mean apnea-hypopnea index of atypical parkinsonism with RBD (AP-RBD) group was 16.2 ± 17.7 events/h (MSA-RBD, 14.0 ± 16.6; DLB-RBD, 18.8 ± 19.1), which was significantly higher than the other groups (p < 0.05). The proportion of patients with 100% supine sleep in the AP-RBD group (44%) was higher than that in the iRBD group (14%; p = 0.030). The proportion of OSA with 100% supine sleep position was significantly higher in the MSA-RBD and DLB-RBD groups than in the iRBD group (p = 0.042 and p = 0.029, respectively)., Conclusion: Our study demonstrated that patients in the MSA-RBD and DLB-RBD groups had a tendency to sleeping in the supine position and a higher vulnerability to OSA compared to other RBD groups. Further cohort studies are needed to evaluate the influence of these factors on the development of parkinsonism., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: This study was aimed to investigate gastrointestinal (GI) dysfunction in patients with Parkinson's disease (PD) compared with those in patients with other parkinsonian disorders, and to characterize parkinsonian motor and non-motor correlates for GI dysfunction., Methods: Consecutive patients with PD, atypical parkinsonism (P-plus) and vascular parkinsonism (VP) were enrolled in this multicenter systematic survey. Data for weight loss, appetite loss, sialorrhea, dysphagia, gastroesophageal reflux disease (GERD) and constipation were simultaneously collected using symptom-specific, structured questionnaires. For the PD group, information for onset age, PD duration, anti-parkinsonian drug dosages, unified PD rating scale, and Hoehn & Yahr stage were collected at the time of the interview., Results: Enrolled in the study were 329 PD, 82 P-plus, and 62 VP patients. GI symptom frequencies were similar in PD and other parkinsonian groups. Among the PD patients, constipation was the most common symptom, followed by appetite loss, weight loss, dysphagia, sialorrhea, and GERD (64.9%, 45.4%, 35.7%, 19.4%, 15.0%, and 9.6%, respectively). Dysphagia, sialorrhea, and constipation became more frequent with more advanced PD stages. Cognition, sleep and mood disturbances were significantly associated with weight loss, appetite loss, and dysphagia, whereas bradykinesia, axial and postural instability with gait disturbance were associated with dysphagia., Conclusions: GI disturbance is common in patients with non-PD parkinsonism as well as in those with PD. GI symptoms correlated with distinct parkinsonian motor and nonmotor features in PD. Further studies are warranted to reveal the pathophysiological mechanisms and prognostic features of GI disturbances in parkinsonian disorders., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

To evaluate the diagnostic value of putaminal abnormality on 3-T magnetic resonance imaging (MRI) for differentiating early parkinsonism-predominant multiple system atrophy (MSA-p) from Parkinson disease (PD) based on long-term clinical follow-up data. Totals of 23 clinical MSA-p (6 possible and 17 suspicious) and 50 PD patients were included. Subjects submitted to 3-T MRI at baseline and were followed up to substantiate the initial diagnosis. MRI findings were compared between MSA-p and PD patients based on the final diagnosis. Putaminal abnormalities were recorded as presence of atrophy, signal hypointensity, and abnormal disruption of the hyperintense lateral rim of the putamen. The sum scores for putaminal abnormality were calculated from the presence of each item. During the follow-up over 3 years, the diagnosis of MSA-p was supported in 17 patients (14 probable and 3 possible) and the diagnosis of PD was stable in all 50 patients. Putaminal abnormalities were more frequent in MSA-p (n = 17) than in PD (n = 50). A sum score of >1 on 3-T MRI had sensitivity, specificity, and positive- and negative-predictive values of 70.6, 93, 77.4, and 90.3%, respectively, for differentiating MSA-p from PD. Fourteen of the initial 23 clinical MSA-p patients had a sum score of >1, and in all but two, the diagnosis became supported during the follow-up, whereas the diagnosis of five of the nine patients with a sum score of ≤1 remained uncertain. Putaminal abnormality on 3-T MRI can be a specific diagnostic marker for early stage MSA-p.

We report a 38-year-old Korean man with sporadic rapid-onset dystonia-parkinsonism (RDP), who had a Thr 618 Met mutation in the Na(+)/K(+)-ATPase alpha3 subunit gene (ATP1A3). At the age of 21, he acutely developed severe dystonia and parkinsonism, which rapidly deteriorated into a wheelchair-bound state within 4 days. He is the first Asian RDP patient confirmed by genetic testing, ascertaining that RDP gene mutation is present in Asians. Pathophysiological considerations are briefly discussed., ((c) 2007 Movement Disorder Society.)

Introduction: SCA17 is an autosomal dominant cerebellar ataxia with expansion of the CAG/CAA trinucleotide repeats in the TATA-binding protein (TBP) gene. SCA17 can have various clinical presentations including parkinsonism, ataxia, chorea and dystonia. SCA17 is diagnosed by detecting the expanded CAG repeats in the TBP gene; however, in the literature, pathologic repeat numbers as low as 41 overlap with normal repeat numbers. Methods: The subjects in this study included patients with involuntary movement disorders such as cerebellar ataxia, parkinsonism, chorea and dystonia who visited Seoul National University Hospital between Jan. 2006 and Apr. 2014 and were screened for SCA17. Those who were diagnosed with other genetic diseases or nondegenerative diseases were excluded. DNA from healthy subjects who did not have a family history of parkinsonism, ataxia, psychiatric symptoms, chorea or dystonia served as the control. In total, 5242 chromosomes from 2099 patients and 522 normal controls were analyzed. Results: The total number of patients included in the analysis was 2099 (parkinsonism, 1706; ataxia, 345; chorea, 37; and dystonia, 11). In the normal control, up to 44 repeats were found. In the 44 repeat group, there were 7 (0.3%) patients and 1 (0.2%) normal control. In 43 repeat group, there were 8 (0.4%) patients and 2 (0.4%) normal controls. In the 42 repeat group, there were 16 (0.8%) patients and 3 (0.6%) normal controls. In 41 repeat group, there were 48 (2.3%) patients and 8 (1.5%) normal controls. Considering the overlaps and non-significant differences in allelic frequencies between the patients and the normal controls with low-expansions, we could not determine a definitive cutoff value for the pathologic CAG repeat number of SCA17. Conclusion: Because the statistical analysis between the normal controls and patients with low range expansions failed to show any differences so far, we must consider that clinical cases with low range expansions could be idiopathic movement disorders showing coincidental CAG/CAA expansions. Thus, we need to reconsider the pathologic role of low range expansions (41–42). Long term follow up and comprehensive investigations using autopsy and imaging studies in patients and controls with low range expansions are necessary to determine the cutoff value for the pathologic CAG repeat number of SCA17. [ABSTRACT FROM AUTHOR]

Abstract: Background: Multiple system atrophy (MSA) rarely begins before the age of 40 and detailed descriptions of young-onset MSA are lacking. Methods: Among 455 patients included in our MSA cohort, four developed disease before the age of 40. We reviewed the medical records of these patients. Results: Case 1 and 2 presented with cerebellar symptoms. Case 1 had clinical features and a course typical of MSA. Case 2 had a rapid course and died 3years after onset. Case 3 and Case 4 presented with levodopa-responsive parkinsonism. Both developed motor fluctuations and peak-dose limb dyskinesias. Subthalamic deep brain stimulation (DBS) resulted in some improvements in motor symptoms, but they became totally dependent within a few years. Discussion: Young-onset MSA is rare but does exist. Young-onset MSA with predominant parkinsonism may closely resemble Parkinson disease at onset and is likely to develop motor complications. Attention should be given to the possibility of young-onset MSA in selecting DBS candidates. [Copyright &y& Elsevier]