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.

Internal Representations Are Prioritized by Frontoparietal Theta Connectivity and Suppressed by alpha Oscillation Dynamics: Evidence from Concurrent Transcranial Magnetic Stimulation EEG and Invasive EEG.

Control over internal representations requires the prioritization of relevant information and suppression of irrelevant information. The frontoparietal network exhibits prominent neural oscillations during these distinct cognitive processes. Yet, the causal role of this network-scale activity is unclear. Here, we targeted theta-frequency frontoparietal coherence and dynamic alpha oscillations in the posterior parietal cortex using online rhythmic transcranial magnetic stimulation (TMS) in women and men while they prioritized or suppressed internally maintained working memory (WM) representations. Using concurrent high-density EEG, we provided evidence that we acutely drove the targeted neural oscillation and TMS improved WM capacity only when the evoked activity corresponded with the desired cognitive process. To suppress an internal representation, we increased the amplitude of lateralized alpha oscillations in the posterior parietal cortex contralateral to the irrelevant visual field. For prioritization, we found that TMS to the prefrontal cortex increased theta-frequency connectivity in the prefrontoparietal network contralateral to the relevant visual field. To understand the spatial specificity of these effects, we administered the WM task to participants with implanted electrodes. We found that theta connectivity during prioritization was directed from the lateral prefrontal to the superior posterior parietal cortex. Together, these findings provide causal evidence in support of a model where a frontoparietal theta network prioritizes internally maintained representations and alpha oscillations in the posterior parietal cortex suppress irrelevant representations.

Effects of different levels of dietary crude protein on growth performance, blood profiles, diarrhea incidence, nutrient digestibility, and odor emission in weaning pigs.

OBJECTIVE: This experiment was conducted to evaluate the effects of different levels of dietary crude protein (CP) on growth performance, blood profiles, diarrhea incidence, nutrient digestibility, and odor emission in weaning pigs. METHODS: A total of 240 weaning ([Yorkshire×Landrace]×Duroc) pigs (8.25±0.050 kg body weight [BW]) were assigned to six treatments based on sex and initial BW, with five replicates of eight pigs per pen in a randomized complete block design. Experimental diets with different crude protein levels for early and late weaning phases were as follows: i) CP16, corn‒soybean-based diet containing 16%/15% CP; ii) CP17, corn‒soybean-based diet containing 17%/16% CP; iii) CP18, corn‒soybean-based diet containing 18%/17% CP; iv) CP19, corn‒soybean-based diet containing 19%/18% CP; v) CP20, corn‒soybean-based diet containing 20%/19% CP; and vi) CP21, corn‒soybean-based diet containing 21%/20% CP. RESULTS: In the early weaning period, average daily feed intake increased when the dietary CP level decreased (linear, p<0.05). During the entire experimental period, average daily gain and the gain to feed ratio decreased when the dietary CP level increased (linear, p< 0.01). Additionally, a decrease in dietary CP level resulted in a linear increase in final BW (linear, p<0.05). In the early and late weaning periods, blood urea nitrogen (BUN) decreased when the dietary CP level decreased (linear, p<0.01). There were no significant differences in creatinine, glucose, total protein, triglyceride or insulin-like factor-1 levels over the experimental period. The concentrations of immunoglobulin A (IgA) and IgG were not significantly affected by dietary CP levels during the experimental period. In the early weaning period, fecal and urine N decreased when the dietary CP level decreased (linear, p<0.01). No differences in nutrient digestibility among the treatments during the early weaning period were found. Throughout the whole experimental period, when the dietary CP level decreased in the weaning pig diet, the diarrhea incidence decreased linearly (linear, p<0.01). Throughout the whole experimental period, when the dietary CP level decreased in the weaning pig diet, ammonia, amines and hydrogen sulfide decreased linearly (linear, p<0.01). CONCLUSION: Reducing dietary CP could decrease diarrhea incidence, the concentration of BUN in serum and odor emission in manure. Furthermore, it could improve N excretion in feces and urine and growth performance in weaning pigs.

Prediction of amyloid PET positivity via machine learning algorithms trained with EDTA-based blood amyloid-ß oligomerization data.

BACKGROUND: The tendency of amyloid-ß to form oligomers in the blood as measured with Multimer Detection System-Oligomeric Amyloid-ß (MDS-OAß) is a valuable biomarker for Alzheimer's disease and has been verified with heparin-based plasma. The objective of this study was to evaluate the performance of ethylenediaminetetraacetic acid (EDTA)-based MDS-OAß and to develop machine learning algorithms to predict amyloid positron emission tomography (PET) positivity. METHODS: The performance of EDTA-based MDS-OAß in predicting PET positivity was evaluated in 312 individuals with various machine learning models. The models with various combinations of features (i.e., MDS-OAß level, age, apolipoprotein E4 alleles, and Mini-Mental Status Examination [MMSE] score) were tested 50 times on each dataset. RESULTS: The random forest model best-predicted amyloid PET positivity based on MDS-OAß combined with other features with an accuracy of 77.14 ± 4.21% and an F1 of 85.44 ± 3.10%. The order of significance of predictive features was MDS-OAß, MMSE, Age, and APOE. The Support Vector Machine using the MDS-OAß value only showed an accuracy of 71.09 ± 3.27% and F-1 value of 80.18 ± 2.70%. CONCLUSIONS: The Random Forest model using EDTA-based MDS-OAß combined with the MMSE and apolipoprotein E status can be used to prescreen for amyloid PET positivity.

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.

Clinical Aspects of the Differential Diagnosis of Parkinson's Disease and Parkinsonism.

Parkinsonism is a clinical syndrome presenting with bradykinesia, tremor, rigidity, and postural instability. Nonmotor symptoms have recently been included in the parkinsonian syndrome, which was traditionally associated with motor symptoms only. Various pathologically distinct and unrelated diseases have the same clinical manifestations as parkinsonism or parkinsonian syndrome. The etiologies of parkinsonism are classified as neurodegenerative diseases related to the accumulation of toxic protein molecules or diseases that are not neurodegenerative. The former class includes Parkinson's disease (PD), multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Over the past decade, clinical diagnostic criteria have been validated and updated to improve the accuracy of diagnosing these diseases. The latter class of disorders unrelated to neurodegenerative diseases are classified as secondary parkinsonism, and include drug-induced parkinsonism (DIP), vascular parkinsonism, and idiopathic normal-pressure hydrocephalus (iNPH). DIP and iNPH are regarded as reversible and treatable forms of parkinsonism. However, studies have suggested that the absence of protein accumulation in the nervous system as well as managing the underlying causes do not guarantee recovery. Here we review the differential diagnosis of PD and parkinsonism, mainly focusing on the clinical aspects. In addition, we describe recent updates to the clinical criteria of various disorders sharing clinical symptoms with parkinsonism.

Sensory tricks modulate corticocortical and corticomuscular connectivity in cervical dystonia.

OBJECTIVE: To examine interactions between cortical areas and between cortical areas and muscles during sensory tricks in cervical dystonia (CD). METHODS: Thirteen CD patients and thirteen age-matched healthy controls performed forewarned reaction time tasks, sensory tricks, and two tasks replicating aspects of the tricks (moving necks/arms). Control subjects mimicked sensory tricks. Corticocortical and corticomuscular coherence values were calculated from surface electrodes placed over motor, premotor, and sensory cortical areas and dystonic muscles. RESULTS: During initial preparation (after the warning stimulus), the only between-task difference was found in the γ-band corticocortical coherence (higher during tricks than during voluntary neck movements). With movements (before/after the imperative stimulus), the γ-band coherence of CD patients significantly increased during tricks but decreased during voluntary movements, while opposite trends were observed in healthy subjects. Additionally, the α- and ß-band coherence decreased in healthy subjects during movements. Between the two patient subgroups (typical vs. forcible tricks), only those with typical tricks showed significant decrease in corticomuscular coherence during tricks. CONCLUSIONS: Observed changes in the corticocortical coherence suggest that sensory tricks improve cortical function, which reduces corticomuscular connectivity and the dystonia. SIGNIFICANCE: We demonstrated that sensory tricks fundamentally affect sensorimotor integration in CD, both in movement preparation and execution.

Evaluation of Dietary Curcumin Nanospheres in a Weaned Piglet Model.

Curcumin is a polyphenolic compound present in turmeric with extensive uses in cooking foods and biomedical applications. However, due to its hydrophobic nature, it is poorly soluble in water and its bioavailability is very low on oral administration in organisms. In this study, we investigated the dietary curcumin nanospheres in a weaned piglet model based on the growth, serum biochemistry, proteomics, fecal coliform bacteria, and malodors in the feces of piglets. A total of 135 weaned piglets (Duroc × [Yorkshire × Landrace]) with an average initial body weight of 7.0 ± 1.0 kg (28 ± 1 days of age) were randomly distributed in 9 pens (15 pigs in each pen) fed the dietary curcumin nanospheres (CN) at 0 (control), 0.5 (T1), and 1.0 mL (T2) CN/kg of diet in triplicates for 21 days. At the end of the feeding trial, the results showed piglets fed 1.0 mL CN/kg diet had significantly higher growth performance and feed utilization than control diet (without CN). However, there were no significant differences in growth and feed utilization between piglets fed T1 and T2 diets. Serum glucose, gamma-glutamyl transferase, total bilirubin, amylase, and lipase contents were unaffected in piglets fed the experimental diets. Interestingly, piglets fed T1 and T2 diets showed significantly lower total cholesterol levels than control diet. In serum proteomics, a total of 103 differentially expressed proteins (DEPs) were identified in the piglets fed control, T1, and T2 diets, of which 14 DEPs were upregulated and 4 DEPs were downregulated. Fecal coliform bacteria and ammonia gas were significantly reduced in piglets fed T1 and T2 diets. Overall, the results indicated dietary supplementation of CN could enhance the growth, feed utilization, and immunity-and reduce fecal pathogenic bacteria as well as ammonia gas emissions-in weaned piglets.

Use of the Clock Drawing Test and the Rey-Osterrieth Complex Figure Test-copy with convolutional neural networks to predict cognitive impairment.

BACKGROUND: The Clock Drawing Test (CDT) and Rey-Osterrieth Complex Figure Test (RCFT) are widely used as a part of neuropsychological test batteries to assess cognitive function. Our objective was to confirm the prediction accuracies of the RCFT-copy and CDT for cognitive impairment (CI) using convolutional neural network algorithms as a screening tool. METHODS: The CDT and RCFT-copy data were obtained from patients aged 60-80 years who had more than 6 years of education. In total, 747 CDT and 980 RCFT-copy figures were utilized. Convolutional neural network algorithms using TensorFlow (ver. 2.3.0) on the Colab cloud platform ( www.colab. RESEARCH: google.com ) were used for preprocessing and modeling. We measured the prediction accuracy of each drawing test 10 times using this dataset with the following classes: normal cognition (NC) vs. mildly impaired cognition (MI), NC vs. severely impaired cognition (SI), and NC vs. CI (MI + SI). RESULTS: The accuracy of the CDT was better for differentiating MI (CDT, 78.04 ± 2.75; RCFT-copy, not being trained) and SI from NC (CDT, 91.45 ± 0.83; RCFT-copy, 90.27 ± 1.52); however, the RCFT-copy was better at predicting CI (CDT, 77.37 ± 1.77; RCFT, 83.52 ± 1.41). The accuracy for a 3-way classification (NC vs. MI vs. SI) was approximately 71% for both tests; no significant difference was found between them. CONCLUSIONS: The two drawing tests showed good performance for predicting severe impairment of cognition; however, a drawing test alone is not enough to predict overall CI. There are some limitations to our study: the sample size was small, all the participants did not perform both the CDT and RCFT-copy, and only the copy condition of the RCFT was used. Algorithms involving memory performance and longitudinal changes are worth future exploration. These results may contribute to improved home-based healthcare delivery.

Sensory tricks in cervical dystonia correlate with enhanced brain activity during motor preparation.

INTRODUCTION: Although sensory tricks are well known as the maneuvers that temporarily relieve dystonic symptoms in patients with cervical dystonia (CD), the underlying neurophysiological mechanisms remain unclear. We aimed to investigate brain potentials related to sensory tricks in patients with CD. METHODS: Thirteen patients with CD and 13 age-matched healthy volunteers participated. The experiment consisted of three conditions (moving the neck, moving an arm, and performing sensory tricks) presented in different blocks in random order in a contingent negative variation (CNV) paradigm. Warning and trigger stimuli (S1 and S2) were presented to the participants, who were instructed to prepare to perform the specific task for each condition after S1, and then to perform the task after S2. Early and late components of the CNV were measured. RESULTS: The late CNVs in patients with CD were significantly larger than those in healthy participants in Fz, FCz, Cz, and C3 electrodes. Only in patients with CD, the late CNVs were significantly greater for the 'sensory tricks' condition compared to the 'move neck' condition in Fz and C3 electrodes. CONCLUSION: The late CNV is increased during sensory tricks in patients with CD, suggesting that sensory tricks may affect mechanisms related to the motor preparatory phase in the premotor and primary motor areas. Sensory tricks may normalize impaired motor preparation in dystonia, leading to improved dystonic symptoms.

Inosine 5'-Monophosphate to Raise Serum Uric Acid Level in Multiple System Atrophy (IMPROVE-MSA study).

The aim of this trial was to investigate the safety, tolerability, and capability of serum uric acid (UA) elevation of inosine 5'-monophosphate (IMP) in multiple system atrophy (MSA). The IMPROVE-MSA trial was a randomized, double-blind, placebo-controlled trial in patients with MSA with no history of hyperuricemia-related disorders. The participants were assigned to placebo (n = 25) or IMP (n = 30) in a 1 to 1 ratio, and then followed up for 24 weeks. The primary end points included safety, tolerability, and alteration of the serum UA level during the follow-up period. The secondary end points were changes in scores of the unified MSA rating scale (UMSARS) and the Mini-Mental Status Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The total number of adverse events (AEs) and serious AEs was comparable between the active and placebo groups. Serum UA level (mg/dL) was significantly increased from baseline (active vs. placebo, 4.57 vs. 4.58; P = 0.98) to study end point (6.96 vs. 4.43; P < 0.001) in the active group compared with the placebo group (time × group interaction; P < 0.001). The change in UMSARS scores did not differ between the active and placebo groups. However, the active group showed better alterations in MoCA scores with nominal significance (P < 0.001) and tendency for better alterations in MMSE scores (P = 0.09) than the placebo group. Our data demonstrated that IMP treatment was generally safe and well-tolerated in patients with MSA. A further trial with a long-term follow-up is required to examine whether UA elevation will slow clinical progression in early MSA.

Astrocyte deletion of α2-Na/K ATPase triggers episodic motor paralysis in mice via a metabolic pathway.

Familial hemiplegic migraine is an episodic neurological disorder characterized by transient sensory and motor symptoms and signs. Mutations of the ion pump α2-Na/K ATPase cause familial hemiplegic migraine, but the mechanisms by which α2-Na/K ATPase mutations lead to the migraine phenotype remain incompletely understood. Here, we show that mice in which α2-Na/K ATPase is conditionally deleted in astrocytes display episodic paralysis. Functional neuroimaging reveals that conditional α2-Na/K ATPase knockout triggers spontaneous cortical spreading depression events that are associated with EEG low voltage activity events, which correlate with transient motor impairment in these mice. Transcriptomic and metabolomic analyses show that α2-Na/K ATPase loss alters metabolic gene expression with consequent serine and glycine elevation in the brain. A serine- and glycine-free diet rescues the transient motor impairment in conditional α2-Na/K ATPase knockout mice. Together, our findings define a metabolic mechanism regulated by astrocytic α2-Na/K ATPase that triggers episodic motor paralysis in mice.

Neuropsychiatric Symptoms and Quality of Life in Patients With Adult-Onset Idiopathic Focal Dystonia and Essential Tremor.

Background: While idiopathic focal dystonia (IFD) and essential tremor (ET) have been considered pure movement disorders, they reportedly induce neuropsychiatric manifestations and may thus be more accurately described as network disorders. Methods: The present multi-center, cross-sectional, case-control study evaluated the severity of depression and anxiety with the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI), respectively; the frequency of neuropsychiatric disorders with the Korean-Mini International Neuropsychiatry Interview; and QoL with the Short-Form 36 (SF-36). Results: Seventy-four subjects participated in this study (IFD, 27; ET, 24; controls, 23). The BDI and BAI scores were higher in the IFD and ET groups than in the control group. Although the frequency of neuropsychiatric disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Axis I was comparable among the groups, the prevalence of major depressive disorder tended to be high among patients with IFD. QoL was correlated with the severity of depression and anxiety across the groups. Conclusions: Depression and anxiety are more severe in patients with IFD and ET compared to healthy controls, while their severity is similar among patients with IFD and ET. Axis I major depressive disorder is relatively more prevalent in patients with IFD. Neuropsychiatric symptoms affect QoL regardless of the affected individual's condition, addressing neuropsychiatric symptoms in patients with movement disorders may be crucial to improving their QoL.

Dysautonomia Is Linked to Striatal Dopamine Deficits and Regional Cerebral Perfusion in Early Parkinson Disease.

PURPOSE: The aim of this study was to investigate the association between autonomic dysfunction and striatal dopamine depletion or metabolic changes in de novo Parkinson disease (PD). METHODS: Based on the Composite Autonomic Severity Score (CASS), patients with de novo PD were classified into PD with (PD-AUT+) and without autonomic dysfunction (PD-AUT-) groups. We compared the dopamine transporter (DAT) availability in the striatum by quantitatively measuring F-FP-CIT PET between both groups. We also assessed the association between DAT availability and the CASS. In addition, we compared regional uptake in early-phase images of F-FP-CIT PET as well as cortical thickness between the PD-AUT+ and PD-AUT- groups. RESULTS: The PD-AUT+ group had significantly lower DAT availability in all striatal subregions than did the PD-AUT- group. The total CASS was significantly correlated with DAT availability in all striatal subregions. In addition, the subscores of the adrenergic component were correlated with DAT availability in all striatal subregions. The subscores of the cardiovagal component were negatively correlated with DAT availability in the caudate and ventral striatum. In early-phase F-FP-CIT PET, the PD-AUT+ group exhibited decreased regional perfusion in the parieto-occipital areas and increased regional perfusion in the pallidothalamic, pontocerebellar, inferior frontal, and primary motor areas compared with the PD-AUT- group. There were no regions of different cortical thickness between the PD groups. CONCLUSIONS: The present study revealed that autonomic dysfunction is closely linked to striatal dopamine depletion and prominent PD-related perfusion patterns in de novo PD, suggesting a greater pathological burden in patients with dysautonomia.

Long-term Effects of Bilateral Subthalamic Deep Brain Stimulation on Postural Instability and Gait Difficulty in Patients with Parkinson's Disease.

OBJECTIVE: The long-term effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on postural instability and gait difficulty (PIGD) in patients with Parkinson's disease (PD) remain unclear. In this study, we aimed to evaluate the longterm effects of STN-DBS surgery on PIGD symptoms in patients with advanced-stage PD. METHODS: This study included 49 consecutively included patients with PD who underwent bilateral STN-DBS. The Unified Parkinson's Disease Rating Scale (UPDRS) scores and subscores for PIGD were assessed at baseline and at 1, 3, and 5 years postoperatively. The PIGD subscore was divided into PIGD-motor and PIGD-activities of daily living (ADL) scores according to parts III and II of the UPDRS, respectively. RESULTS: The PIGD-motor and PIGD-ADL scores at the "medication-off" state improved at 3 and 5 years, respectively. Overall, the UPDRS III and II scores at "medication-off" improved at 5 years. The UPDRS IV score also significantly improved and the levodopa equivalent daily dosage decreased at all follow-ups. Finally, the PIGD-motor score at baseline was able to predict long-term improvement in the PIGD-motor score at the 5-year follow-up. CONCLUSION: The STN-DBS has both short- and long-term effects on PIGD, as well as overall motor function, in patients with advanced PD. The degree of PIGD at the preoperative evaluation can be used to predict long-term outcomes after STN-DBS surgery.

Prevalence and incidence of Parkinson's disease and drug-induced parkinsonism in Korea.

BACKGROUND: Parkinson's disease (PD) and drug-induced parkinsonism (DIP) are the major diseases of parkinsonism. To better understand parkinsonism, we aimed to assess the prevalence and incidence of PD and DIP in Korea from 2012 to 2015. METHODS: We used the Health Insurance Review and Assessment Service database, which covers the entire population in Korea. We used claims during 2011-2015 to assess epidemiology of PD and DIP during 2012-2015. Retrospective cross-sectional study design was employed to assess prevalence, whereas retrospective cohort study design was used to determine incidence. Patients with at least one claim with ICD-10 G20 and who received antiparkinsonian drugs for at least 60 days were classified as having PD. We excluded patients with antiparkinsonian drugs that can be used for indications other than PD. Patients with at least one claim with ICD-10 G211 or G251 during the prescription period of drugs that are frequently related with DIP were classified as having DIP. Incident cases had a disease-free period of 1 year before diagnosis. To evaluate the significance of changes in the prevalence or incidence over time, Poisson regression was used to determine p for trend. RESULTS: The prevalence of PD increased from 156.9 per 100,000 persons in 2012 to 181.3 per 100,000 persons in 2015 (p for trend< 0.0001). The incidence of PD decreased steadily from 35.4 per 100,000 person-years in 2012 to 33.3 per 100,000 person-years in 2015 (p for trend< 0.0001). The prevalence of DIP increased from 7.3 per 100,000 persons in 2012 to 15.4 per 100,000 persons in 2015 (p for trend< 0.0001) and the incidence of DIP increased from 7.1 per 100,000 person-years in 2012 to 13.9 per 100,000 person-years in 2015 (p for trend< 0.0001). CONCLUSIONS: Our study suggests that the incidence of PD has gradually decreased whereas, the incidence of DIP increased from 2012 to 2015. Further studies are warranted to examine possible causes of increased DIP incidence in order to develop management strategy for parkinsonism.

Focal Leg Dystonia Associated with Cerebellar Infarction and Application of Low-Frequency Cerebellar Transcranial Magnetic Stimulation: Evidence of Topographically Specific Cerebellar Contribution to Dystonia Development.

The cerebellum has recently been highlighted as a key neural substrate responsible for dystonia. A 57-year-old female presented with isolated focal leg dystonia that developed 8 years after acute cerebellar infarction. Brain magnetic resonance imaging showed an old cerebellar infarct in the right anterior cerebellum. Low-frequency cerebellar repetitive transcranial magnetic stimulation on the right cerebellum partially improved dystonia in this patient. This case provides valuable evidence on cerebellar mechanisms related to the development of dystonia in a topographically specific manner. Cerebellar brain stimulation can be a potential therapeutic strategy for patients with dystonia.