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Basal Ganglia Syndrome in a Male With an XK Gene Variant but Without XK Disease (McLeod Syndrome)
Jeryl Ritzi T. Yu, Ruth H. Walker, Adrian Danek, Connie M. Westhoff, Sunitha Vege, Ilia Itin
J Mov Disord. 2024;17(2):226-229.   Published online January 8, 2024
DOI: https://doi.org/10.14802/jmd.23196
Funded: European Multidisciplinary Initiative on Neuroacanthocytosis, Ludwig-Maximilians-Universität Munich, Germany
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Hemimasticatory Spasm Treated With Muscle Afferent Block Therapy and Occlusal Splint
Kazuya Yoshida
J Mov Disord. 2024;17(2):230-232.   Published online January 15, 2024
DOI: https://doi.org/10.14802/jmd.23249
Funded: Japan Society for the Promotion of Science, KAKENHI
  • 921 View
  • 38 Download
  • 1 Web of Science
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  • Hemimasticatory spasm: a series of 17 cases and a comprehensive review of the literature
    Kazuya Yoshida
    Frontiers in Neurology.2024;[Epub]     CrossRef
A Case of 18p Chromosomal Deletion Encompassing GNAL in a Patient With Dystonia-Parkinsonism
Giulia Di Rauso, Francesco Cavallieri, Edoardo Monfrini, Alessandro Fraternali, Valentina Fioravanti, Sara Grisanti, Annalisa Gessani, Isabella Campanini, Andrea Merlo, Giulia Toschi, Manuela Napoli, Rosario Pascarella, Rosamaria Silipigni, Palma Finelli, Jefri J. Paul, Peter Bauer, Annibale Versari, Alessio Di Fonzo, Franco Valzania
J Mov Disord. 2024;17(2):236-238.   Published online January 23, 2024
DOI: https://doi.org/10.14802/jmd.23222
Funded: Italian Ministry of Health
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Case Report
Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry
Shen-Yang Lim, Ai Huey Tan, Jia Nee Foo, Yi Jayne Tan, Elaine GY Chew, Azlina Ahmad Annuar, Alfand Marl Dy Closas, Azalea Pajo, Jia Lun Lim, Yi Wen Tay, Anis Nadhirah, Jia Wei Hor, Tzi Shin Toh, Lei Cheng Lit, Jannah Zulkefli, Su Juen Ngim, Weng Khong Lim, Huw R. Morris, Eng-King Tan, Adeline SL Ng
J Mov Disord. 2024;17(2):213-217.   Published online January 31, 2024
DOI: https://doi.org/10.14802/jmd.24009
Funded: Ministry of Higher Education Malaysia, University of Malaya Parkinson’s Disease, Ministry of Health’s National Medical Research Council, Ministry of Education , Open Fund Large Collaborative, Singapore Translational Research, Clinician-Scientist Award, Precision Medicine Research, Singapore
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AbstractAbstract PDFSupplementary Material
Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

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  • Parkinson’s Disease is Predominantly a Genetic Disease
    Shen-Yang Lim, Christine Klein
    Journal of Parkinson's Disease.2024; 14(3): 467.     CrossRef
Original Articles
Comparing Montreal Cognitive Assessment Performance in Parkinson’s Disease Patients: Age- and Education-Adjusted Cutoffs vs. Machine Learning
Kyeongmin Baek, Young Min Kim, Han Kyu Na, Junki Lee, Dong Ho Shin, Seok-Jae Heo, Seok Jong Chung, Kiyong Kim, Phil Hyu Lee, Young H. Sohn, Jeehee Yoon, Yun Joong Kim
J Mov Disord. 2024;17(2):171-180.   Published online February 13, 2024
DOI: https://doi.org/10.14802/jmd.23271
Funded: Korea Health Industry Development Institute, Ministry of Health and Welfare, National Research Foundation of Korea, Ministry of Science and ICT
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AbstractAbstract PDFSupplementary Material
Objective
The Montreal Cognitive Assessment (MoCA) is recommended for general cognitive evaluation in Parkinson’s disease (PD) patients. However, age- and education-adjusted cutoffs specifically for PD have not been developed or systematically validated across PD cohorts with diverse education levels.
Methods
In this retrospective analysis, we utilized data from 1,293 Korean patients with PD whose cognitive diagnoses were determined through comprehensive neuropsychological assessments. Age- and education-adjusted cutoffs were formulated based on 1,202 patients with PD. To identify the optimal machine learning model, clinical parameters and MoCA domain scores from 416 patients with PD were used. Comparative analyses between machine learning methods and different cutoff criteria were conducted on an additional 91 consecutive patients with PD.
Results
The cutoffs for cognitive impairment decrease with increasing age within the same education level. Similarly, lower education levels within the same age group correspond to lower cutoffs. For individuals aged 60–80 years, cutoffs were set as follows: 25 or 24 years for those with more than 12 years of education, 23 or 22 years for 10–12 years, and 21 or 20 years for 7–9 years. Comparisons between age- and education-adjusted cutoffs and the machine learning method showed comparable accuracies. The cutoff method resulted in a higher sensitivity (0.8627), whereas machine learning yielded higher specificity (0.8250).
Conclusion
Both the age- and education-adjusted cutoff methods and machine learning methods demonstrated high effectiveness in detecting cognitive impairment in PD patients. This study highlights the necessity of tailored cutoffs and suggests the potential of machine learning to improve cognitive assessment in PD patients.
High Levels of Mutant Huntingtin Protein in Tear Fluid From Huntington’s Disease Gene Expansion Carriers
Marlies Gijs, Nynke Jorna, Nicole Datson, Chantal Beekman, Cira Dansokho, Alexander Weiss, David E. J. Linden, Mayke Oosterloo
J Mov Disord. 2024;17(2):181-188.   Published online February 21, 2024
DOI: https://doi.org/10.14802/jmd.24014
Funded: VICO Therapeutics B.V.
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  • 185 Download
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AbstractAbstract PDFSupplementary Material
Objective
Huntington’s disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects middle-aged adults. HD is caused by a CAG repeat expansion in the HTT gene, resulting in the expression of mutant huntingtin (mHTT). Our aim was to detect and quantify mHTT in tear fluid, which, to our knowledge, has never been measured before.
Methods
We recruited 20 manifest and 13 premanifest HD gene expansion carriers, and 20 age-matched controls. All patients underwent detailed assessments, including the Unified Huntington’s Disease Rating Scale (UHDRS) total motor score (TMS) and total functional capacity (TFC) score. Tear fluid was collected using paper Schirmer’s strips. The level of tear mHTT was determined using single-molecule counting SMCxPRO technology.
Results
The average tear mHTT levels in manifest (67,223 ± 80,360 fM) and premanifest patients (55,561 ± 45,931 fM) were significantly higher than those in controls (1,622 ± 2,179 fM). We noted significant correlations between tear mHTT levels and CAG repeat length, “estimated years to diagnosis,” disease burden score and UHDRS TMS and TFC. The receiver operating curve demonstrated an almost perfect score (area under the curve [AUC] = 0.9975) when comparing controls to manifest patients. Similarly, the AUC between controls and premanifest patients was 0.9846. The optimal cutoff value for distinguishing between controls and manifest patients was 4,544 fM, whereas it was 6,596 fM for distinguishing between controls and premanifest patients.
Conclusion
Tear mHTT has potential for early and noninvasive detection of alterations in HD patients and could be integrated into both clinical trials and clinical diagnostics.

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  • Unveiling brain disorders using liquid biopsy and Raman spectroscopy
    Jeewan C. Ranasinghe, Ziyang Wang, Shengxi Huang
    Nanoscale.2024;[Epub]     CrossRef
Effectiveness of Live-Streaming Tele-Exercise Intervention in Patients With Parkinson’s Disease: A Pilot Study
Jongmok Ha, Jung Hyun Park, Jun Seok Lee, Hye Young Kim, Ji One Song, Jiwon Yoo, Jong Hyeon Ahn, Jinyoung Youn, Jin Whan Cho
J Mov Disord. 2024;17(2):189-197.   Published online February 29, 2024
DOI: https://doi.org/10.14802/jmd.23251
Funded: Korea Disease Control and Prevention Agency
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AbstractAbstract PDFSupplementary Material
Objective
Exercise can improve both motor and nonmotor symptoms in people with Parkinson’s disease (PwP), but there is an unmet need for accessible and sustainable exercise options. This study aimed to evaluate the effect, feasibility, and safety of a regularly performed live-streaming tele-exercise intervention for PwP.
Methods
A live-streaming exercise intervention for PwP was implemented twice a week for 12 weeks. We measured the motor and nonmotor symptom scores of the included patients before and after the intervention. Changes in clinical scores from baseline to postintervention were analyzed using paired t-tests. Factors associated with improvements in clinical scores and compliance were analyzed using Pearson’s correlation analysis.
Results
Fifty-six participants were enrolled in the study. There were significant improvements in Hospital Anxiety and Depression Scale (HADS)-anxiety (p = 0.007), HADS-depression (p < 0.001), Unified Parkinson’s Disease Rating Scale (UPDRS) part III (p < 0.001), UPDRS total (p = 0.015), Hoehn and Yahr stage (p = 0.027), and Parkinson’s Disease Fatigue Scale-16 (p = 0.026) scores after the intervention. Improvements in motor symptoms were associated with improvements in mood symptoms and fatigue. Higher motor impairment at baseline was associated with a greater compliance rate and better postintervention composite motor and nonmotor outcomes (ΔUPDRS total score). Overall, the 12-week tele-exercise program was feasible and safe for PwP. No adverse events were reported. The overall adherence rate was 60.0% in our cohort, and 83.4% of the participants were able to participate in more than half of the exercise routines.
Conclusion
The live-streaming tele-exercise intervention is a safe, feasible, and effective nonpharmacological treatment option that can alleviate fatigue and improve mood and motor symptoms in PwP.
Fasting Plasma Glucose Levels and Longitudinal Motor and Cognitive Outcomes in Parkinson’s Disease Patients
Ko-Eun Choi, Dong-Woo Ryu, Yoon-Sang Oh, Joong-Seok Kim
J Mov Disord. 2024;17(2):198-207.   Published online March 6, 2024
DOI: https://doi.org/10.14802/jmd.23264
Funded: National Research Foundation of Korea, Ministry of Science, ICT and Future Planning, Korea “National Institute of Health” research project
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AbstractAbstract PDFSupplementary Material
Objective
Hyperglycemia and diabetes mellitus have been identified as poor prognostic factors for motor and nonmotor outcomes in patients with Parkinson’s disease (PD), although there is some controversy with this finding. In the present study, we investigated the effects of fasting plasma glucose (FPG) levels on longitudinal motor and cognitive outcomes in PD patients.
Methods
We included a total of 201 patients who were diagnosed with PD between January 2015 and January 2020. The patients were categorized based on FPG level into euglycemia (70 mg/dL < FPG < 100 mg/dL), intermediate glycemia (100 mg/dL ≤ FPG < 126 mg/dL), and hyperglycemia (FPG ≥ 126 mg/dL), and longitudinal FPG trajectories were analyzed using group-based trajectory modeling. Survival analysis was conducted to determine the time until motor outcome (Hoehn and Yahr stage ≥ 2) and the conversion from normal cognition to mild cognitive impairment.
Results
Among the patient cohort, 82 had euglycemia, 93 had intermediate glycemia, and 26 had hyperglycemia. Intermediate glycemia (hazard ratio 1.747, 95% confidence interval [CI] 1.083–2.816, p = 0.0221) and hyperglycemia (hazard ratio 3.864, 95% CI 1.996–7.481, p < 0.0001) were found to be significant predictors of worsening motor symptoms. However, neither intermediate glycemia (hazard ratio 1.183, 95% CI 0.697–2.009, p = 0.5339) nor hyperglycemia (hazard ratio 1.297, 95% CI 0.601–2.800, p = 0.5078) demonstrated associations with the longitudinal progression of cognitive impairment. Diabetes mellitus, defined by self-reported medical history, was not related to poor motor or cognitive impairment outcomes.
Conclusion
Our results suggest that both impaired glucose tolerance and hyperglycemia could be associated with motor progression in PD patients.
Viewpoint
A Practical Guide for Clinical Approach to Patients With Huntington’s Disease in Korea
Chaewon Shin, Ryul Kim, Dallah Yoo, Eungseok Oh, Jangsup Moon, Minkyeong Kim, Jee-Young Lee, Jong-Min Kim, Seong-Beom Koh, Manho Kim, Beomseok Jeon
J Mov Disord. 2024;17(2):138-149.   Published online March 12, 2024
DOI: https://doi.org/10.14802/jmd.24040
Funded: Seoul National University Boramae Medical Center, Chungnam National University Hospital
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Review Article
α-Synuclein: A Promising Biomarker for Parkinson’s Disease and Related Disorders
Taku Hatano, Ayami Okuzumi, Gen Matsumoto, Taiji Tsunemi, Nobutaka Hattori
J Mov Disord. 2024;17(2):127-137.   Published online April 9, 2024
DOI: https://doi.org/10.14802/jmd.24075
Funded: Japan Agency for Medical Research and Development, Scientific Research, Japan Society for the Promotion of Science, Visionary Council, Research Committee of CNS Degenerative Disease, Health, Labor, and Welfare Sciences Research Grants, Ministry of Health, Labour and Welfare
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AbstractAbstract PDF
Mutations in the SNCA gene, which encodes α-synuclein (α-syn), play a key role in the development of genetic Parkinson’s disease (PD). α-Syn is a major component of Lewy bodies in PD and glial cytoplasmic inclusions in multiple system atrophy (MSA). Rapid eye movement sleep behavior disorder patients often progress to PD, dementia with Lewy bodies, or MSA, which are collectively known as α-synucleinopathies. The loss of dopaminergic neurons with Lewy bodies precedes motor dysfunction in these diseases, but the mechanisms of neurodegeneration due to α-syn aggregation are poorly understood. Monitoring α-syn aggregation in vivo could serve as a diagnostic biomarker and help elucidate pathogenesis, necessitating a simple and accurate detection method. Seed amplification assays (SAAs), such as real-time quaking-induced conversion and protein misfolding cyclic amplification, are used to detect small amounts of abnormally structured α-syn protofibrils, which are central to aggregation. These methods are promising for the early diagnosis of α-synucleinopathy. Differences in α-syn filament structures between α-synucleinopathies, as observed through transmission electron microscopy and cryo-electron microscopy, suggest their role in the pathogenesis of neurodegeneration. SAAs may differentiate between subtypes of α-synucleinopathy and other diseases. Efforts are also being made to identify α-syn from blood using various methods. This review introduces body fluid α-syn biomarkers based on pathogenic α-syn seeds, which are expected to redefine α-synucleinopathy diagnosis and staging, improving clinical research accuracy and facilitating biomarker development.
Original Article
Caregiver Burden of Patients With Huntington’s Disease in South Korea
Chan Young Lee, Chaewon Shin, Yun Su Hwang, Eungseok Oh, Manho Kim, Hyun Sook Kim, Sun Ju Chung, Young Hee Sung, Won Tae Yoon, Jin Whan Cho, Jae-Hyeok Lee, Han-Joon Kim, Hee Jin Chang, Beomseok Jeon, Kyung Ah Woo, Seong-Beom Koh, Kyum-Yil Kwon, Jangsup Moon, Young Eun Kim, Jee-Young Lee
J Mov Disord. 2024;17(1):30-37.   Published online September 11, 2023
DOI: https://doi.org/10.14802/jmd.23134
Funded: Seoul National University
  • 2,660 View
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AbstractAbstract PDFSupplementary Material
Objective
This is the first prospective cohort study of Huntington’s disease (HD) in Korea. This study aimed to investigate the caregiver burden in relation to the characteristics of patients and caregivers.
Methods
From August 2020 to February 2022, we enrolled patients with HD from 13 university hospitals in Korea. We used the 12-item Zarit Burden Interview (ZBI-12) to evaluate the caregiver burden. We evaluated the clinical associations of the ZBI-12 scores by linear regression analysis and investigated the differences between the low- and high-burden groups.
Results
Sixty-five patients with HD and 45 caregivers were enrolled in this cohort study. The average age at onset of motor symptoms was 49.3 ± 12.3 years, with an average cytosine-adenine-guanine (CAG)n of 42.9 ± 4.0 (38–65). The median ZBI-12 score among our caregivers was 17.6 ± 14.2. A higher caregiver burden was associated with a more severe Shoulson–Fahn stage (p = 0.038) of the patients. A higher ZBI-12 score was also associated with lower independence scale (B = -0.154, p = 0.006) and functional capacity (B = -1.082, p = 0.002) scores of patients. The caregiving duration was longer in the high- than in the low-burden group. Caregivers’ demographics, blood relation, and marital and social status did not affect the burden significantly.
Conclusion
HD patients’ neurological status exerts an enormous impact on the caregiver burden regardless of the demographic or social status of the caregiver. This study emphasizes the need to establish an optimal support system for families dealing with HD in Korea. A future longitudinal analysis could help us understand how disease progression aggravates the caregiver burden throughout the entire disease course.

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  • A Practical Guide for Clinical Approach to Patients With Huntington’s Disease in Korea
    Chaewon Shin, Ryul Kim, Dallah Yoo, Eungseok Oh, Jangsup Moon, Minkyeong Kim, Jee-Young Lee, Jong-Min Kim, Seong-Beom Koh, Manho Kim, Beomseok Jeon
    Journal of Movement Disorders.2024; 17(2): 138.     CrossRef
Letter to the editor
Factors associated with anticholinergic-induced oral-buccal-lingual dyskinesia in Parkinson’s disease
Joonyoung Ha, Suk Yun Kang, Kyoungwon Baik, Young H. Sohn, Phil Hyu Lee, Min Seok Baek, Jin Yong Hong
J Mov Disord. 2024;17(1):109-111.   Published online September 22, 2023
DOI: https://doi.org/10.14802/jmd.23069
Funded: National Research Foundation of Korea, Ministry of SMEs and Startups, Ministry of Trade, Industry and Energy
  • 907 View
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PDFSupplementary Material
Original Articles
Retinal Thinning as a Marker of Disease Severity in Progressive Supranuclear Palsy
Yueting Chen, Haotian Wang, Bo Wang, Wenbo Li, Panpan Ye, Wen Xu, Peng Liu, Xinhui Chen, Zhidong Cen, Zhiyuan Ouyang, Sheng Wu, Xiaofeng Dou, Yi Liao, Hong Zhang, Mei Tian, Wei Luo
J Mov Disord. 2024;17(1):55-63.   Published online September 26, 2023
DOI: https://doi.org/10.14802/jmd.23102
Funded: Science and Technology Department of Zhejiang Province, Zhejiang Province
  • 1,698 View
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AbstractAbstract PDFSupplementary Material
Objective
Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort.
Methods
We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism.
Results
The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate.
Conclusion
The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

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  • Optical Coherence Tomography as a Biomarker in the Differential Diagnosis between Parkinson’s Disease and Atypical Parkinsonian Syndromes: A Narrative Review
    Stella Karatzetzou, Dimitrios Parisis, Serafeim Ioannidis, Theodora Afrantou, Panagiotis Ioannidis
    Applied Sciences.2024; 14(6): 2491.     CrossRef
Comparative Olfactory Profiles in Parkinson’s Disease and Drug-Induced Parkinsonism
In Hee Kwak, Young Eun Kim, Suk Yun Kang, Joong Seob Lee, Jeongjae Lee, Min Seung Kim, Dong A Yea, Hyeo-il Ma
J Mov Disord. 2024;17(1):64-70.   Published online October 6, 2023
DOI: https://doi.org/10.14802/jmd.23105
Funded: Korea Health Industry Development Institute, Ministry of Health and Welfare, National Research Foundation of Korea
  • 1,434 View
  • 164 Download
AbstractAbstract PDFSupplementary Material
Objective
Drug-induced parkinsonism (DIP) is a frequently encountered diagnostic possibility when considering Parkinson’s disease (PD). While olfactory dysfunction is a common clinical feature in PD, the comparison of olfactory function between the two conditions remains insufficient. This study aimed to compare olfactory function, including threshold, discrimination, and identification (TDI) profiles, between PD and DIP.
Methods
Consecutive patients with drug-naïve PD (n = 78) or DIP (n = 31) confirmed through dopamine transporter imaging were enrolled in this study. The YSK olfactory function (YOF) test, composed of TDI domains culturally familiar odorants to Koreans, was administered to all patients.
Results
In the study population, patients with DIP were significantly older than patients with PD. Over 70% of patients in each group had hyposmia or anosmia, and there was no significant difference in the occurrence of olfactory dysfunction between the two groups. In addition, there were no differences in the total YOF score and threshold score between the two groups. Meanwhile, the PD group had a significantly lower discrimination and identification score than the DIP group after adjusting for age, sex, the existence of diabetes, disease duration, and cognitive function.
Conclusion
This study demonstrated that detailed olfactory profiles are different in PD and DIP, even though olfactory dysfunction can be observed in both conditions.
Letter to the editor
A Case of Task-Specific Tremor of the Hand While Driving
Minkyeong Kim, Eunji Kim, Seok Min Moon, Juhyeon Kim, Heeyoung Kang
J Mov Disord. 2024;17(1):112-114.   Published online October 12, 2023
DOI: https://doi.org/10.14802/jmd.23175
Funded: National Research Foundation of Korea, Ministry of Science and ICT
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