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Abstract Despite the association between spinal cord injury (SCI) and various neurological diseases, the risk of Parkinson’s disease (PD) in SCI is not elucidated yet. Especially, the role of SCI severity and injury level in the risk of PD development is not investigated. Based on the nation-wide cohort data the Korean National Health Insurance Service between 2010 and 2018, we investigated the incidence of PD in 7,182 patients with SCI compared with 24,844 age- and sex-matched controls. Adjusted hazard ratio and 95% confidence interval (CI) were calculated using Cox proportional hazards regression. We compared the risk of PD based on the degree of disability (without disability, mild, severe) and SCI level (cervical, thoracic, and lumbar). During the mean follow-up duration of 4.31 years, patients with SCI had a higher risk of PD compared with matched controls. The PD risk was greater among patients with SCI with disability than in those without disability, especially those with mild disability. Additionally, cervical-level injury was associated with the highest risk in patients with SCI without disability, while thoracic-level injury was associated with the highest risk in those with disability. Our study found patients with SCI have increased risk of PD, particularly those with disability and thoracic-level injuries.

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.

Abstract Stridor is a rare but important non-motor symptom that can support the diagnosis and prediction of worse prognosis in multiple system atrophy. Recording sounds generated during sleep by video-polysomnography is recommended for detecting stridor, but the analysis is labor intensive and time consuming. A method for automatic stridor detection should be developed using technologies such as artificial intelligence (AI) or machine learning. However, the rarity of stridor hinders the collection of sufficient data from diverse patients. Therefore, an AI method with high diagnostic performance should be devised to address this limitation. We propose an AI method for detecting patients with stridor by combining audio splitting and reintegration with few-shot learning for diagnosis. We used video-polysomnography data from patients with stridor (19 patients with multiple system atrophy) and without stridor (28 patients with parkinsonism and 18 patients with sleep disorders). To the best of our knowledge, this is the first study to propose a method for stridor detection and attempt the validation of few-shot learning to process medical audio signals. Even with a small training set, a substantial improvement was achieved for stridor detection, confirming the clinical utility of our method compared with similar developments. The proposed method achieved a detection accuracy above 96% using data from only eight patients with stridor for training. Performance improvements of 4%–13% were achieved compared with a state-of-the-art AI baseline. Moreover, our method determined whether a patient had stridor and performed real-time localization of the corresponding audio patches, thus providing physicians with support for interpreting and efficiently employing the results of this method.

Tardive dyskinesia (TD) is a movement disorder that can arise as a side effect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinical management of this challenging condition are scarce. However, neurologists have an essential role in managing the movement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally.

IntroductionSubjective cognitive complaints (SCC) refer to self-reported cognitive decline that may or may not be reflected in objective neuropsychological evaluations. Such SCC are prevalent in neurodegenerative diseases, including Parkinson’s disease (PD), but the prevalence and clinical features in patients with progressive supranuclear palsy (PSP) have not been investigated.MethodsWe recruited 83 PSP patients without dementia and investigated their SCC using a semi-structured interview. Comprehensive neuropsychological test results and patient clinical features were compared according to presence of SCC and underlying cognitive state.ResultsAmong the 83 patients, 16 had normal cognition (NC), 67 had mild cognitive impairment (MCI), and 36 (43.4%) reported SCC. Among NC patients, 37.5% (6/16) had SCC, while 44.8% (30/67) of MCI patients reported SCC. There were no differences between the neuropsychological test results or demographic and clinical characteristics of PSP patients with or without SCC in the NC group. The demographic and clinical characteristics of the MCI+SCC (MCI with SCC)and MCI-SCC (MCI without SCC) groups were comparable, but the MCI+SCC group had significantly worse neuropsychological scores than the MCI-SCC group, particularly in tests assessing attention, language, visual memory, and fronto-executive function domains.DiscussionWhile SCC are commonly reported by PSP patients, patients with PSP and MCI+SCC had worse cognitive function than those who did not report SCC. These findings suggest that SCC in PSP patients with MCI could be a worsening sign of cognitive function. Therefore, it is crucial for physicians to assess SCC in PSP patients and to provide timely diagnosis and management of cognitive decline.

Abstract Orthostatic hypotension (OH) is a common non-motor symptom in Parkinson’s disease (PD). OH can cause cerebral and retinal hypoperfusion and is associated with microvascular damage in PD. Optical coherence tomography angiography (OCTA) is a non-invasive technology that can be used to visualize the retinal microvasculature and detect microvascular damage in PD. In the present study, 51 PD patients (OH+, n = 20, 37 eyes; OH−, n = 32, 61 eyes) and 51 healthy controls (100 eyes) were evaluated. The Unified Parkinson’s Disease Rating Scale III, Hoehn and Yahr scale, Montreal Cognitive Assessment, levodopa equivalent daily dose, and vascular risk factors, including hypertension, diabetes, and dyslipidemia, were investigated. PD patients underwent a head-up tilt (HUT) test. The PD patients had a lower superficial retinal capillary plexus (SRCP) density in the central region than control patients. The PDOH+ group had lower vessel density in the SRCP of the central region compared with the control group and lower vessel density in the DRCP of the central region than the PDOH− and control groups. The changes in systolic and diastolic blood pressure during the HUT test in PD patients showed a negative correlation with the vessel density in the DRCP central region. The presence of OH was a critical factor associated with central microvasculature damage in PD. These findings indicate that OCTA can be a useful and non-invasive tool for detecting microvasculature damage in PD patients.

Abstract Automated segmentation and volumetry of brain magnetic resonance imaging (MRI) scans are essential for the diagnosis of Parkinson’s disease (PD) and Parkinson’s plus syndromes (P-plus). To enhance the diagnostic performance, we adopt deep learning (DL) models in brain MRI segmentation and compared their performance with the gold-standard non-DL method. We collected brain MRI scans of healthy controls ( $$n=105$$ n = 105 ) and patients with PD ( $$n=105$$ n = 105 ), multiple systemic atrophy ( $$n=132$$ n = 132 ), and progressive supranuclear palsy ( $$n=69$$ n = 69 ) at Samsung Medical Center from January 2017 to December 2020. Using the gold-standard non-DL model, FreeSurfer (FS), we segmented six brain structures: midbrain, pons, caudate, putamen, pallidum, and third ventricle, and considered them as annotated data for DL models, the representative convolutional neural network (CNN) and vision transformer (ViT)-based models. Dice scores and the area under the curve (AUC) for differentiating normal, PD, and P-plus cases were calculated to determine the measure to which FS performance can be reproduced as-is while increasing speed by the DL approaches. The segmentation times of CNN and ViT for the six brain structures per patient were 51.26 ± 2.50 and 1101.82 ± 22.31 s, respectively, being 14 to 300 times faster than FS (15,735 ± 1.07 s). Dice scores of both DL models were sufficiently high (> 0.85) so their AUCs for disease classification were not inferior to that of FS. For classification of normal vs. P-plus and PD vs. P-plus (except multiple systemic atrophy - Parkinsonian type) based on all brain parts, the DL models and FS showed AUCs above 0.8, demonstrating the clinical value of DL models in addition to FS. DL significantly reduces the analysis time without compromising the performance of brain segmentation and differential diagnosis. Our findings may contribute to the adoption of DL brain MRI segmentation in clinical settings and advance brain research.

BackgroundWaiting impulsivity in progressive supranuclear palsy-Richardson’s syndrome (PSP-RS) is difficult to assess, and its regulation is known to involve nucleus accumbens (NAc) subregions. We investigated waiting impulsivity using the “jumping the gun” (JTG) sign, which is defined as premature initiation of clapping before the start signal in the three-clap test and compared clinical features of PSP-RS patients with and without the sign and analyzed neural connectivity and microstructural changes in NAc subregions.Materials and methodsA positive JTG sign was defined as the participant starting to clap before the start sign in the three-clap test. We classified participants into the JTG positive (JTG +) and JTG negative (JTG-) groups and compared their clinical features, microstructural changes, and connectivity between NAc subregions using diffusion tension imaging. The NAc was parcellated into core and shell subregions using data-driven connectivity-based methods.ResultsSeventy-seven patients with PSP-RS were recruited, and the JTG + group had worse frontal lobe battery (FAB) scores, more frequent falls, and more occurrence of the applause sign than the JTG- group. A logistic regression analysis revealed that FAB scores were associated with a positive JTG sign. The mean fiber density between the right NAc core and right medial orbitofrontal gyrus was higher in the JTG + group than the JTG- group.DiscussionWe show that the JTG sign is a surrogate marker of waiting impulsivity in PSP-RS patients. Our findings enrich the current literature by deepening our understanding of waiting impulsivity in PSP patients and introducing a novel method for its evaluation.

Safinamide is a selective, reversible, monoamine oxidase B inhibitor for the treatment of patients with Parkinson's disease (PD) and motor fluctuations. This was a post hoc analysis of the SETTLE study, in which patients with PD and motor fluctuations were randomly assigned to 24-week treatment with safinamide (50 mg/day for 2 weeks, increased to 100 mg/day if tolerated) or placebo. In the present analysis, responders were defined according to their treatment responses at Week 2 and Week 24 based on changes in ON-time without troublesome dyskinesia from baseline with cutoffs of 1 hour. It was found that 81% (103/127) of the responders at Week 2 maintained the response through Week 24 in the safinamide group. Other outcomes did not necessarily coincide with the ON-time response; however, “Early” responders who showed a treatment response at both Week 2 and Week 24 had substantial improvements from baseline in OFF-time, UPDRS Part II and III scores, and PDQ-39 summary index scores through Week 24. The safinamide group had a higher proportion of early responders than the placebo group (39% vs 20%, p < 0.0001). At baseline, early responders in the safinamide group had significantly higher UPDRS Part II and III scores, shorter ON-time, and longer OFF-time than the other responder populations. In conclusion, the results of the present post hoc analysis suggest that patients with a short ON-time, severe motor symptoms, and highly compromised activities of daily living can benefit from safinamide early in treatment and over the long term.

Introduction. Fatigue and orthostatic hypotension (OH) are common and disabling nonmotor symptoms (NMSs) of Parkinson’s disease (PD), but none of the studies have reported on the longitudinal association between fatigue and OH. Methods. Drug-naïve PD patients were recruited from a hospital-based cohort and evaluated with the Parkinson Fatigue Scale (PFS), head-up tilt test, Unified PD Rating Scale, Hoehn and Yahr stage, Montreal Cognitive Assessment, Scale for Outcomes in PD-Autonomic (SCOPA-AUT), Beck Depression Inventory (BDI), Beck Anxiety Inventory, PD Sleep Scale, and medications at the baseline and follow-up visits. Results. A total of 80 patients were included, and the mean ages were 66.6 and 63.8 years in the fatigue and nonfatigue groups, respectively. The prevalence of fatigue was 17.5% (14/80) at the baseline and follow-up (mean follow-up: 23.3 ± 9.9 months). The prevalence of OH in the fatigue group was 57.1%, and it was significantly higher than that of the nonfatigue group. Six of the 14 patients (42.9%) in the fatigue group had persistent fatigue at the follow-up, and eight of them (57.1%) converted to the nonfatigue group. Logistic regression analysis demonstrated that the changes of BDI and the presence of OH at the baseline were the predictors for fatigue in drug-naïve PD. Conclusion. Fatigue is a common NMS in PD but can vary depending on the disease course. OH and depression are the most relevant predictors for the development of fatigue in drug-naïve PD. The present study suggests that the management of autonomic symptoms and depression might be helpful for managing fatigue in PD.

BackgroundDysphagia is an important non-motor symptom that is closely associated with quality of living and mortality in Parkinson's disease (PD). However, the pathophysiology of dysphagia in PD remains inconclusive. We tried to confirm whether the occurrence of dysphagia could be related to sympathetic degeneration using cardiac 123I-metaiodobenzylguanidine (MIBG) scintigraphy.MethodsWe prospectively recruited 27 PD patients and classified them into two groups (PD with dysphagia vs. PD without dysphagia) by Swallowing Disturbance Questionnaire (SDQ) score and compared the clinical characteristics, videofluoroscopic swallowing study (VFSS) findings and parameters from cardiac MIBG scintigraphy.ResultsThe mean early and late H/M ratios were significantly lower in the PD with dysphagia group than those in the PD without dysphagia group (1.39 ± 0.21 vs. 1.86 ± 0.21, p < 0.01; 1.26 ± 0.18 vs. 1.82 ± 0.29, p < 0.01). In the correlation analysis, both the early and late H/M ratios were negatively correlated with the SDQ score and total VDS score (r = −0.65, p < 0.01; r = −0.53, p < 0.01; r = −0.65, p < 0.01, r = −0.58, p < 0.01).ConclusionWe confirmed that cardiac sympathetic denervation might be associated with the presence and severity of dysphagia. This finding indicates that dysphagia in PD could be associated with a nondopaminergic mechanism.

Abstract Fatigue is a common and disabling non-motor symptom (NMS) of Parkinson’s disease (PD); however, it has been poorly understood in patients with progressive supranuclear palsy (PSP). We investigated the association between fatigue, clinical features, and other NMS in patients with probable PSP. In 72 probable PSP patients, fatigue was investigated using the Parkinson Fatigue Scale (PFS). Further, all patients were evaluated using the PSP rating scale (PSPRS), Beck Depression Inventory (BDI), Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), PD Sleep Scale (PDSS), NMS scale (NMSS), PD Questionnaire-39 summary index (PDQ-39 SI), and Scale for outcomes in PD-Autonomic (SCOPA-AUT). The prevalence of fatigue assessed by PFS was 38.9% (28/72) in patients with PSP. The secondary fatigue was defined as fatigued patients with depression and/or sleep disturbances. We divided the patients into primary (n = 15), secondary (n = 13), and non-fatigue groups. There were no differences in age, sex, disease duration, and PSPRS, PDSS, MMSE, and FAB scores among the three groups. The primary fatigue group had higher scores in PDQ-39 SI compared to the non-fatigue group. The secondary fatigue group showed higher scores in NMSS, PDQ-39 SI, and SCOPA-AUT compared to the non-fatigue group. PFS was positively correlated with NMSS and PDQ-39 SI and SCOPA-AUT. Fatigue is common in patients with PSP and is associated with the NMS and the quality of life in these patients. The present study provides meaningful insight into fatigue in patients with PSP.

BackgroundStudies 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 MethodsA 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.ResultsThe 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).ConclusionsThis 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.

BackgroundDespite the clinical impact of levodopa-induced dyskinesia (LID) in Parkinson's disease (PD), the mechanism, especially the role of basal ganglia (BG), is not fully elucidated yet. We investigated the BG structural changes related to LID in PD using a surface-based shape analysis technique.MethodsWe recruited patients with PD who developed LID within 3 years (LID group, 28 patients) and who did not develop it after 7 years (non-LID group, 35 patients) from levodopa treatment for the extreme case-control study. BG structure volumes were measured using volumetry analysis and the surface-based morphometry feature (i.e., Jacobian) from the subcortical surface vertices. We compared the volume and Jacobian of meshes in the regions between the two groups. We also performed a correlation analysis between local atrophy and the severity of LID. Additionally, we evaluated structural connectivity profiles from globus pallidus interna and externa (GPi and GPe) to other brain structures based on the group comparison.ResultsThe demographic and clinical data showed no significant difference except for disease duration, treatment duration, parkinsonism severity, and levodopa equivalent dose. The LID group had more local atrophies of vertices in the right GPi than the non-LID group, despite no difference in volumes. Furthermore, the LID group demonstrated significantly reduced structural connectivity between left GPi and thalamus.ConclusionThis is the first demonstration of distinct shape alterations of basal ganglia structures, especially GPi, related to LID in PD. Considering both direct and indirect BG pathways share the connection between GPi and thalamus, the BG pathway plays a crucial role in the development of LID.

BackgroundGait problems are critical impairments in Parkinson's disease (PD) and are related to increased risk of fall and negatively impact activities of daily life. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that can modify the cortical excitability of gait-related brain regions. In this study, we investigated whether multichannel tDCS with simultaneous treadmill gait training could improve gait in PD.MethodsTwenty-four patients with PD were assigned randomly to a real or sham tDCS group. Before intervention, one patient of the real tDCS group was dropped out, leaving 23 patients to be analyzed in this study. Each patient underwent 30 min of treadmill gait training for 10 sessions over four consecutive weeks. Multichannel 4x1 tDCS was applied using five 6-cm-diameter round electrodes. One anode was placed on the CZ, and four cathodes were positioned symmetrically over the FZ, C5, C6, and PZ. Anodal tDCS (2mA) and sham tDCS were delivered for 20 min. The secondary outcomes were gait performance, as measured by the timed up and go test (TUG) and freezing of gait questionnaire (FOG-Q), and balance was assessed using the dynamic gait index (DGI), Berg balance scale (BBS), and functional reach test (FRT). Motor and non-motor performance of patients with PD were assessed using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Participants were assessed before the intervention, immediately after the intervention, and 4 weeks after completion of the intervention.ResultsThe real tDCS group showed a significant improvement in the 10-m walk test, but the sham group did not. Among the secondary outcome measures, MDS-UPDRS part II, TUG, and BBS were improved only in the real tDCS group. Particularly, MDS-UPDRS part II showed a significant group*time interaction effect, indicating that real tDCS demonstrated a better effect on the activities of daily living patients with PD.ConclusionsThe results of this pilot study suggest that multichannel tDCS applied on the leg motor cortex during treadmill gait training is a safe and effective means to improve gait velocity in patients with PD. Additional rigorous, large-sample, multicenter, randomized controlled trials are needed to confirm the effect of tDCS as a therapeutic adjunct for gait rehabilitation of patients with PD.

Although the KMT2B gene was identified as a causative gene for early-onset generalized dystonia, the efficacy of deep brain stimulation (DBS) in KMT2B-related dystonia has not been clearly elucidated. Here, we describe a 28-year-old woman who developed generalized dystonia with developmental delay, microcephaly, short stature, and cognitive decline. She was diagnosed with KMT2B- related dystonia using whole-exome sequencing with a heterozygous frameshift insertion of c.515dupC (p.T172fs) in the KMT2B gene. Oral medications and botulinum toxin injection were not effective. The dystonia markedly improved with bilateral pallidal DBS (the Burke-Fahn-Marsden Dystonia Rating Scale score was reduced from 30 to 5 on the dystonia movement scale and from 11 to 1 on the disability scale), and she could walk independently. From this case, we suggest that bilateral globus pallidus internus DBS can be an effective treatment option for patients with KMT2B-related generalized dystonia.

Abstract Backgrounds Although the short‐term efficacy of bilateral subthalamic deep brain stimulation (DBS) has been reported in a limited number of Parkinson's disease (PD) patients with SNCA mutations, there are no data for long‐term outcome. Methods This multicenter retrospective study investigated previously reported PD patients with SNCA mutations, implanted with bilateral subthalamic DBS. We compared demographic and clinical data at baseline and last follow‐up. Clinical data of motor and nonmotor symptoms and motor fluctuation were collected up to 10 years from DBS surgery. Results Among four subjects, three had SNCA duplication and one had c.158C.A (p.A53E) mutation. The mean post‐implantation follow‐up duration was 5.4 ± 3.7 years. All patients with SNCA duplication showed favorable outcome, although one died from breast cancer 1.5 years after DBS. The patient with the missense mutation became wheelchair‐bound due to progressed axial, cognitive and psychiatric symptoms after 3.5 years from DBS despite the benefit on motor fluctuation. Conclusion Based on findings in our small cohort, subthalamic DBS could be beneficial for motor fluctuation in PD patients with SNCA mutations, especially those with SNCA duplication, and cognitive and psychiatric symptoms are important for the long‐term outcome of subthalamic DBS.

Objective: Pisa syndrome (PS) is a disabling postural deformity in Parkinson’s disease (PD). We aimed to elucidate clinical factors determining the severity and laterality of PS in PD.Methods: In 54 PD patients with PS, we measured the clinical factors that are previously known to contribute to the occurrence of PS as follows: asymmetry of motor symptoms for the evaluation of asymmetric basal ganglia dysfunction, the degree and direction of subjective visual vertical (SVV) tilt for the misperception of body verticality, the canal paresis for unilateral peripheral vestibulopathy, and the tonic electromyographic (EMG) hyperactivity of paraspinal muscles for dystonia. Multivariable linear and logistic regression analyses were conducted to identify the clinical factors associated with the degree of truncal tilt, for the quantification of the severity of PS, and PS tilting to the less affected side, respectively.Results: The multivariable linear regression analyses revealed that the larger degree of SVV tilt (β = 0.29, SE = 0.10, p = 0.005), right-sided SVV tilt (β = 2.32, SE = 0.82, p = 0.007), and higher Hoehn and Yahr (HY) stage (β = 4.01, SE = 1.29, p = 0.003) significantly increased the severity of PS. In the multivariable logistic regression analyses, greater asymmetry of motor symptoms [odds ratio (OR) = 2.01, 95% CI = 1.34–3.49] was significantly associated with PS tilting to the less affected side, while right-sided SVV tilt (OR = 0.02, 95% CI = 0.001–0.21), unilateral canal paresis (OR = 0.06, 95% CI = 0.003–0.79), and higher HY stage (OR = 0.04, 95% CI = 0.002–0.46) were associated with PS tilting to the more affected side.Conclusion: Misperception of verticality, asymmetric basal ganglia dysfunction, unilateral peripheral vestibulopathy, and motor disability are the clinical factors associated with the severity and laterality of PS in patients with PD.

Dysarthria may present during the natural course of many degenerative neurological conditions. Hypokinetic and ataxic dysarthria are common in movement disorders and represent the underlying neuropathology. We developed an artificial intelligence (AI) model to distinguish ataxic dysarthria and hypokinetic dysarthria from normal speech and differentiate ataxic and hypokinetic speech in parkinsonian diseases and cerebellar ataxia. We screened 804 perceptual speech analyses performed in the Samsung Medical Center Neurology Department between January 2017 and December 2020. The data of patients diagnosed with parkinsonian disorders or cerebellar ataxia were included. Two speech tasks (numbering from 1 to 50 and reading nine sentences) were analyzed. We adopted convolutional neural networks and developed a patch-wise wave splitting and integrating AI system for audio classification (PWSI-AI-AC) to differentiate between ataxic and hypokinetic speech. Of the 395 speech recordings for the reading task, 76, 112, and 207 were from normal, ataxic dysarthria, and hypokinetic dysarthria subjects, respectively. Of the 409 recordings of the numbering task, 82, 111, and 216 were from normal, ataxic dysarthria, and hypokinetic dysarthria subjects, respectively. The reading and numbering task recordings were classified with 5-fold cross-validation using PWSI-AI-AC as follows: hypokinetic dysarthria vs. others (area under the curve: 0.92 ± 0.01 and 0.92 ± 0.02), ataxia vs. others (0.93 ± 0.04 and 0.89 ± 0.02), hypokinetic dysarthria vs. ataxia (0.96 ± 0.02 and 0.95 ± 0.01), hypokinetic dysarthria vs. none (0.86 ± 0.03 and 0.87 ± 0.05), and ataxia vs. none (0.87 ± 0.07 and 0.87 ± 0.09), respectively. PWSI-AI-AC showed reliable performance in differentiating ataxic and hypokinetic dysarthria and effectively augmented data to classify the types even with limited training samples. The proposed fully automatic AI system outperforms neurology residents. Our model can provide effective guidelines for screening related diseases and differential diagnosis of neurodegenerative diseases.

Background. Due to the clinical impact of exercise in patients with Parkinson’s disease (PD), management should include personalized and effective exercises according to patient’s PD stage. We investigated the detailed exercise behaviors of patients with mild to advanced PD and compared their patterns between PD with and without postural instability (PI). Methods. We enrolled PD patients from September to December 2019. Clinical data on parkinsonism, exercise behaviors, and Physical Activity Scale of the Elderly (PASE) scores were collected and compared between mild PD without PI (Hoehn–Yahr (HY) stages 1 and 2) and advanced PD with PI (HY stages 3 and 4). Results. In total, 263 PD patients were recruited. The mean exercise frequency was 4.7 ± 2.1 times/week, and the average duration was 7.8 ± 6.7 hours/week. The most common exercise was an aerobic exercise (71.9%) of mild-to-moderate intensity, with active walking being the most common (49.0%). The mild PD patients demonstrated a higher duration and intensity of exercise and more physical activity than the advanced PD patients. However, the frequency of exercise was not significantly different between the two groups. The PASE score was significantly higher in mild PD patients than in advanced PD patients (p

Background: Exercise is an important treatment for Parkinson's disease (PD). Therefore, recognizing determinants of exercise behavior for PD based on disease stage is essential. We sought to find whether the determinants differ based on presence of postural instability (PI), which is indicative of disease stage in PD.Methods: We enrolled patients at Samsung Medical Center from September 2019 to November 2020, who had the ability to perform exercise [modified Hoehn and Yahr (HY) stage ≤ 3]. All the motor and non-motor symptoms were investigated. The exercise of the PD patients was evaluated using the Physical Activity Scale of the Elderly (PASE)-leisure score. We classified patients into PD without PI (HY stage 1 – 2) and PD with PI (HY stage 2.5 – 3) groups. Multivariate linear regression was performed using backward elimination in each group to determine factors associated with PASE-leisure score.Results: A total of 233 patients were enrolled. In the PD without PI group (n = 177), the positive determinant of exercise was Activities-Specific Balance Confidence (ABC) score (β = 0.142, p = 0.032), and the negative determinants were fatigue score (β = −0.228, p = 0.018), female (β = −6.900, p = 0.016) and currently employed status (β = −6.072, p = 0.046). In the PD with PI group (n = 56), the positive determinant was non-motor symptom scale (NMSS) score (β = 0.221, p = 0.017) and disease duration (β = 1.001, p = 0.036), while the negative determinants were UPDRS part 3 score (β = −0.974, p < 0.001), UPDRS part 4 score (β = −2.192, p = 0.002), and age (β = −1.052, p < 0.001).Conclusion: Different motor and non-motor symptoms were associated with the exercise in PD patients with and without PI. When encouraging PD patients to exercise, personalized and different strategies should be applied based on the presence of PI.

Objectives: We aimed to validate the accuracy of blood pressure (BP) measurement using a smartwatch in patients with Parkinson's disease (PD).Materials and Methods: We compared 168 pairs of BP (n = 56) measurements acquired by a smartwatch (SM-R850) with those measured by a sphygmomanometer (reference device).Results: Differences between the smartwatch BP and reference BP measurements were compared. The mean and standard deviation of the differences systolic BP (SBP) and diastolic BP (DBP), measured by smartwatch and reference device, fulfilled both criterion 1 (0.4 ± 4.6 and 1.1 ± 4.5 mm Hg for DBP and SBP, respectively) and criterion 2 (0.2 ± 2.5 and 0.9 ± 2.4 mm Hg for DBP and SBP, respectively) of the BP validation criterion of the International Organization for Standardization.Conclusion: BP measurement using a smartwatch with a photoplethysmography sensor is an accurate and reliable method in patients with PD.

Background: Paraneoplastic chorea is typically a subacute progressive hyperkinetic movement disorder. The mainstay of treatment is managing the underlying neoplasm. However, the clinical course may be variable, and effective symptomatic management can precede the start of cancer treatment. Case report: A 63-year-old man presented with insidious onset, slowly progressive generalized chorea for 1 year, later diagnosed as anti-CV2/CRMP5 autoantibody positive paraneoplastic chorea. His chorea was markedly improved with intravenous amantadine. Discussion: In patients with anti-CV2/CRMP5 autoantibody-related chorea, sequential follow-up of brain magnetic resonance imaging reveals progression from active inflammation to atrophy. Our report highlights the efficacy of intravenous amantadine in paraneoplastic chorea.

Phospholipase A2 group VI (PLA2G6)-associated neurodegeneration (PLAN) is an autosomal recessive neurodegenerative disease with a wide clinical spectrum; however, the genotype-phenotype correlation is unknown. Here, we report different phenotypes in one family with the same genotype. A 28-year-old male presented with slowly progressive gait disturbance with spasticity. Onset occurred at 11 years. Interestingly, his younger brother, a 24-year-old male, presented with progressive Parkinsonism, which began at 22 years. He showed excellent response to levodopa but developed a fluctuating medication response and levodopa-induced dyskinesia 1 year after starting levodopa medication. He also demonstrated hyperreflexia, but no spasticity. Dopamine transporter imaging showed reduced uptake in the bilateral putamen. In whole-exome sequencing and Sanger sequencing, a homozygous pathogenic variant (p. R747W) in the PLA2G6 gene was detected in both cases. Despite different clinical features, both subjects had hyperreflexia during the examination and claval hypertrophy was shown on the brain magnetic resonance imaging.

Objective The aim of this study was to investigate the efficacy of globus pallidus interna deep brain stimulation (GPi-DBS) for treating dystonia due to the GNAL mutation. Methods We provide the first report of a dystonia patient with a genetically confirmed GNAL mutation in the Korean population and reviewed the literature on patients with the GNAL mutation who underwent GPi-DBS. We compared the effectiveness of DBS in patients with the GNAL mutation compared to that in patients with DYT1 and DYT6 in a previous study. Results Patients with the GNAL mutation and those with DYT1 had higher early responder rates (GNAL, 5/5, 100%; DYT1, 7/7, 100%) than did patients with DYT6 (p = 0.047). The responder rates at late follow-up did not differ statistically among the three groups (p = 0.278). The decrease in the dystonia motor scale score in the GNAL group was 46.9% at early follow-up and 63.4% at late follow-up. Conclusion GPi-DBS would be an effective treatment option for dystonia patients with the GNAL mutation who are resistant to medication or botulinum toxin treatment.

Purpose The composite autonomic symptom scale-31 (COMPASS-31) is a self-rated questionnaire that evaluates diverse autonomic symptoms. In the present study, we developed the Korean version of the COMPASS-31 (K-COMPASS-31) with appropriate translation, and verified its reliability and internal and external validity in patients with Parkinson’s disease (PD). Methods The original COMPASS-31 was translated independently into Korean by two bilingual neurologists. Test-retest reliability was evaluated at a 2-week interval. We investigated the correlations between the K-COMPASS-31, the scale for outcomes in PD-autonomic (SCOPA-AUT), and the results of an autonomic function test (AFT), respectively. Results A total of 90 patients with PD (47 females; mean age, 63.4 ± 10.8 years) were enrolled. The K-COMPASS-31 showed excellent test-retest reliability (intra-class correlation coefficient = 0.874, p < 0.001) and internal validity (Cronbach’s α-coefficient = 0.878). The COMPASS-31 was positively correlated with SCOPA-AUT (r = 0.609, p < 0.001) and the results of the AFT. Conclusions In conclusion, the K-COMPASS-31 showed excellent reliability and validity for the assessment of autonomic symptoms in PD patients. The K-COMPASS-31 is an easy-to-repeat and widely used tool for investigating autonomic dysfunction in various neurologic disorders and enables comparison of autonomic dysfunction among neurologic disorders. We recommend the K-COMPASS-31 as a valid instrument for use in clinical practice for patients with PD.

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

Superficial siderosis is a rare disease of the central nervous system, which is characterized by chronic intrathecal hemorrhage leading to hemosiderin deposition on the leptomeninges and subpial layers of the brain and spinal cord. Patients with the syndrome typically present with sensorineural hearing loss, myelopathy, cerebellar ataxia, pyramidal signs, and cognitive impairment. The most common etiologies of the disease include bleeding of unknown cause, ruptured aneurysms, arteriovenous malformation, and traumatic injury of the brain. Here, we describe two patients diagnosed with superficial siderosis caused by spinal lesions, which is an unusual cause of chronic bleeding due to the presence of the disease.

Abstract Falls are a common and disabling symptom in patients with Parkinson’s disease (PD). For prevention, it is important to understand the pathophysiology of falls in PD patients, but the predictors for the possible mechanisms underlying such falls have not been clearly elucidated. In this prospective observational study, we investigated the implications of falling direction to predict the mechanisms of recurrent falls in PD patients. We enrolled 62 recurrent fallers with PD and divided them into two groups according to the main falling directions: 45 PD fallers who fell forward (forward fallers), and 17 PD fallers who fell in the other directions (non-forward fallers). Although there was no difference in demographic data, parkinsonism, or frontal lobe function, forward fallers showed more severe falls and tended to fall during walking or turning, while non-forward fallers usually fell during sitting/standing or turning. Additionally, forward fallers revealed higher score on a freezing of gait (FOG) questionnaire. Logistic regression analysis demonstrated that FOG was associated with falling forward, while balance impairment, akinetic-rigid subtype, and neuropsychiatric symptoms were associated with falling into the other directions. Our results indicate that FOG and balance impairment are two major mechanisms for recurrent falling in PD patients, and falling direction is an important predictor for these mechanisms.

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

Abstract Objectives In screening studies of Western patients with cerebellar dysfunction, FMR1 premutations have been detected. A screening study of East Asian patients with presumed essential tremor (ET) did not detect these mutations, possibly because the ET patients did not closely mimic the phenotype of fragile X‐associated tremor/ataxia syndrome (FXTAS). The aim of this study was to estimate the prevalence of FMR1 premutations in a carefully recruited group of ET patients with additional phenotypic features of FXTAS. Materials and Methods From April 2014 to April 2018, we prospectively recruited patients with ET diagnoses from three tertiary care centers. Demographic and clinical data were collected, as well as data on presence of cerebellar signs and extrapyramidal signs (EPS). Tremor, cerebellar signs, and EPS were evaluated using appropriate clinical rating scales. For ET patients with additional cerebellar signs or EPS, FMR1 mutation analysis and brain magnetic resonance imaging were performed. Results Six hundred and three ET patients were recruited. Cerebellar signs or EPS were present in 168 (27.9%) of 603. FMR1 CGG repeat analysis was performed in 74 of 168 patients. Fifty‐two of 74 had cerebellar signs only, three had EPS only, and 19 had both neurologic abnormalities. Two patients had a FMR1 premutation and fulfiled both clinical and radiological criteria of FXTAS. Conclusions Two (2.7%) of 74 patients with presumed ET and additional neurological features were discovered to have FXTAS. The possibility of FXTAS should be considered in patients with ET who exhibit mild cerebellar signs or EPS.

Objective Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. Methods We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). Results Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. Conclusions We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.

Hereditary ataxia is a heterogeneous disorder characterized by progressive ataxia combined with/without peripheral neuropathy, extrapyramidal symptoms, pyramidal symptoms, seizure, and multiple systematic involvements. More than 35 autosomal dominant cerebellar ataxias have been designated as spinocerebellar ataxia, and there are 55 recessive ataxias that have not been named systematically. Conducting genetic sequencing to confirm a diagnosis is difficult due to the large amount of subtypes with phenotypic overlap. The prevalence of hereditary ataxia can vary among countries, and estimations of prevalence and subtype frequencies are necessary for planning a diagnostic strategy in a specific population. This review covers the various hereditary ataxias reported in the Korean population with a focus on the prevalence and subtype frequencies as the clinical characteristics of the various subtypes.

Differentiation of multiple system atrophy with predominant parkinsonism (MSA-P) and Parkinson's disease (PD) is important, but an effective tool for differentiation has not been identified. We investigated the efficacy of the composite autonomic symptom scale 31 (COMPASS 31) questionnaire as a tool for evaluating autonomic function in parkinsonism patients. In this study, we enrolled drug-naïve patients with MSA-P and PD, and administered the COMPASS-31 and an objective autonomic dysfunction test (AFT). Demographic and clinical data, including parkinsonism and autonomic dysfunction, were compared between the two groups. Additionally, we determined the optimal COMPASS 31 cut-off score to differentiate MSA-P from PD for use as a screening tool. In this study, 27 MSA-P patients and 41 PD patients were recruited. The total COMPASS 31 score was well correlated with the objective AFT results. When we compared the COMPASS 31 score between the two groups, MSA-P patients showed higher total scores and sub-scores in the orthostatic intolerance, gastrointestinal, and bladder domains compared with PD patients. Similarly, MSA-P patients had more abnormalities in expiration to inspiration ratio, Valsalva ratio and pressure recovery time than PD patients in objective AFT. With 13.25 as the cut-off score for diagnosis of MSA-P, the total COMPASS-31 score demonstrated high sensitivity (92.6%) and moderate specificity (51.2%) with an area under the curve of 0.765. Based on our results, the COMPASS 31 is an effective tool for evaluation of autonomic function in patients with parkinsonism. The COMPASS-31 could be used as a sensitive and convenient screening tool, especially for the differentiation between MSA-P and PD.

Despite the clinical impact of non-motor symptoms (NMS) in Parkinson's disease (PD), the characteristic NMS in relation to the motor subtypes of PD is not well elucidated. In this study, we enrolled drug-naïve PD patients and compared NMS between PD subtypes. We enrolled 136 drug-naïve, early PD patients and 50 normal controls. All the enrolled PD patients were divided into tremor dominant (TD) and non-tremor dominant (NTD) subtypes. The Non-Motor Symptom Scale and scales for each NMS were completed. We compared NMS and the relationship of NMS with quality of life between normal controls and PD patients, and between the PD subtypes. Comparing with normal controls, PD patients complained of more NMS, especially mood/cognitive symptoms, gastrointestinal symptoms, unexplained pain, weight change, and change in taste or smell. Between the PD subtypes, the NTD subtype showed higher total NMS scale score and sub-score about weight change. Weight change was the characteristic NMS related to NTD subtype even after controlled other variables with logistic regression analysis. Even from the early stage, PD patients suffer from various NMS regardless of dopaminergic medication. Among the various NMS, weight change is the characteristic NMS associated with NTD subtype in PD patients.

Background and Purpose: Multiple system atrophy with predominant cerebellar ataxia is a disabling neurologic disease. However, effective management has not yet been established. We conducted a short-term, open-label preliminary study to assess the benefits of intravenous amantadine treatment in patients with probable multiple system atrophy with predominant cerebellar ataxia. Methods: Twenty patients (10 male, 10 female) with probable multiple system atrophy with predominant cerebellar ataxia received 400 mg of amantadine by intravenous per day for 5 days. Ataxia severity was evaluated by the International Cooperative Ataxia Rating Scale before and after intravenous amantadine therapy and all subjects reported subjective improvement after intravenous amantadine treatment using a patient global impression scale. We analyzed the total and subscale scores by the ataxia scale and patient global impression scale. Results: The mean age was 57.4 years (range: 47–72) and the mean disease duration was 30.8 months (range: 11–79). The ataxia severity significantly decreased after intravenous amantadine therapy from 42.5 to 37.3 (p < 0.001). The mean patient global impression scale for improvement was 2.9 and there were no side effects of intravenous amantadine treatment observed. When we assessed responders, the duration of intravenous amantadine effect was more than 1 month in 4 subjects of 7 responders. Conclusions: Our findings suggest that intravenous amantadine treatment can be a safe management option in cerebellar ataxia, although the mechanism is unclear. Thus, further double-blind, long-term studies with a larger sample size are needed.

Chorea-acanthocytosis (ChAc) is a neuroacanthocytosis syndrome presenting with severe movement disorders poorly responsive to drug therapy. Case reports suggest that bilateral deep brain stimulation (DBS) of the ventro-postero-lateral internal globus pallidus (GPi) may benefit these patients. To explore this issue, the present multicentre (n=12) retrospective study collected the short and long term outcome of 15 patients who underwent DBS.Data were collected in a standardized way 2-6 months preoperatively, 1-5 months (early) and 6 months or more (late) after surgery at the last follow-up visit (mean follow-up: 29.5 months).Motor severity, assessed by the Unified Huntington's Disease Rating Scale-Motor Score, UHDRS-MS), was significantly reduced at both early and late post-surgery time points (mean improvement 54.3% and 44.1%, respectively). Functional capacity (UHDRS-Functional Capacity Score) was also significantly improved at both post-surgery time points (mean 75.5% and 73.3%, respectively), whereas incapacity (UHDRS-Independence Score) improvement reached significance at early post-surgery only (mean 37.3%). Long term significant improvement of motor symptom severity (≥ 20 % from baseline) was observed in 61.5 % of the patients. Chorea and dystonia improved, whereas effects on dysarthria and swallowing were variable. Parkinsonism did not improve. Linear regression analysis showed that preoperative motor severity predicted motor improvement at both post-surgery time points. The most serious adverse event was device infection and cerebral abscess, and one patient died suddenly of unclear cause, 4 years after surgery.This study shows that bilateral DBS of the GPi effectively reduces the severity of drug-resistant hyperkinetic movement disorders such as present in ChAc.

Tardive dyskinesia (TD) is a movement disorder that can arise as a side efect of treatment with dopamine receptor-blocking agents (DRBAs), including antipsychotic drugs (APDs) used to manage psychotic illnesses. Second-generation APDs (SGAs) are often preferred to first-generation drugs due to their lower propensity to cause TD, however many SGAs-treated patients still develop the condition. Although TD is a global health concern, evidence regarding the occurrence of TD and how it is managed in Asian countries is currently limited. This article reports the results of a systematic review of the published literature on TD focusing on its prevalence, types of patients, knowledge of the condition, causative factors, and usual treatment pathways in clinical practice in Asian countries. Epidemiological data suggest that the prevalence of TD is increasing globally due to an overall rise in APD use, contributing factors being polypharmacy with multiple APDs, the use of higher than necessary doses, and off-label use for non-psychotic indications. Although exact prevalence figures for TD in Asian countries are difficult to define, there is a similar pattern of rising APD use which will result in increasing numbers of TD patients in this region. These issues need to be addressed and strategies developed to minimize TD risk and manage this disabling condition which impacts patients' quality of life and daily functioning. To date, both research into TD has been predominantly psychiatry focused and the perspectives from neurologists regarding the clinicalmanagement of this challenging condition are scarce. However, neurologists have an essential role inmanaging themovement disorders manifestations that characterize TD. Optimum management of TD, therefore, should ideally involve collaboration between psychiatrists and neurologists in joint care pathways, wherever practical. Collaborative pathways are proposed in this article, and the challenges that will need to be addressed in Asian countries to improve the care of people with TD are highlighted, with a focus on the neurologist's viewpoint and the implications for the management of TD globally. [ABSTRACT FROM AUTHOR]