Journal of Movement Disorders

Original Article

Association Between Gait and Dysautonomia in Patients With De Novo Parkinson’s Disease: Forward Gait Versus Backward Gait: Seon-Min Lee, Mina Lee, Eun Ji Lee, Rae On Kim, Yongduk Kim, Kyum-Yil Kwon; J Mov Disord. 2023;16(1):59-67. Published online September 7, 2022; DOI: https://doi.org/10.14802/jmd.22045; Funded: Soonchunhyang University, Konyang University Hospital

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Abstract PDF: Objective
Studies on gait and autonomic dysfunction have been insufficient so far, particularly de novo Parkinson’s disease (PD). The aim of this study was to identify the association between gait dynamics and autonomic dysfunction in patients with de novo PD.
Methods
A total 38 patients with de novo PD were retrospectively included in this study. Details of patients’ dysautonomia were assessed using the Scales for Outcomes in Parkinson’s Disease-Autonomic Dysfunction (SCOPA-AUT). For assessment of gait, a computerized gait analysis was performed using the GAITRite system for forward gait and backward gait. High SCOPA-AUT score (PD-HSAS) group and low SCOPA-AUT score (PD-LSAS) group were identified according to their SCOPA-AUT scores.
Results
Nineteen (50%) patients with high SCOPA-AUT scores above median value (12.5) were assigned into the PD-HSAS group and others were assigned to the PD-LSAS group. Compared with the PD-LSAS group, the PD-HSAS group exhibited slower gait, shorter stride, decreased cadence, increased double support phase, decreased swing phase, and increased variability in swing time. Total SCOPA-AUT score showed significantly positive correlations with gait variability and instability but a negative correlation with gait hypokinesia. In subdomain analysis, urinary dysautonomia was highly associated with impairment of gait dynamics. All significant results were found to be more remarkable in backward gait than in forward gait.
Conclusion
Our findings suggest that alteration in gait dynamics, especially backward gait, is highly associated with autonomic dysfunction in patients with de novo PD.

Review Article

Subjective Cognitive Complaints in Cognitively Normal Patients With Parkinson’s Disease: A Systematic Review: Jin Yong Hong, Phil Hyu Lee; J Mov Disord. 2023;16(1):1-12. Published online November 10, 2022; DOI: https://doi.org/10.14802/jmd.22059; Funded: Ministry of Health & Welfare, Republic of Korea, Korean Healthy Industry Development Institute

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Abstract PDF: Subjective cognitive complaints (SCCs) refer to self-perceived cognitive decline and are related to objective cognitive decline. SCCs in cognitively normal individuals are considered a preclinical sign of subsequent cognitive impairment due to Alzheimer’s disease, and SCCs in cognitively normal patients with Parkinson’s disease (PD) are also gaining attention. The aim of this review was to provide an overview of the current research on SCCs in cognitively normal patients with PD. A systematic search found a lack of consistency in the methodologies used to define and measure SCCs. Although the association between SCCs and objective cognitive performance in cognitively normal patients with PD is controversial, SCCs appear to be predictive of subsequent cognitive decline. These findings support the clinical value of SCCs in cognitively normal status in PD; however, further convincing evidence from biomarker studies is needed to provide a pathophysiological basis for these findings. Additionally, a consensus on the definition and assessment of SCCs is needed for further investigations.

Letter to the editor

Successful Treatment of Biphasic and Peak-dose Dyskinesia With Combined Unilateral Subthalamic Nucleus and Contralateral Globus Pallidus Interna Deep Brain Stimulation: Zhitong Zeng, Zhengyu Lin, Peng Huang, Halimureti Paerhati, Chencheng Zhang, Dianyou Li; J Mov Disord. 2023;16(1):95-97. Published online November 10, 2022; DOI: https://doi.org/10.14802/jmd.22081; Funded: National Natural Science Foundation of China, Shanghai Science and Technology Commission International Cooperation Project

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Review Article

Multiple System Atrophy: Advances in Diagnosis and Therapy: Hirohisa Watanabe, Sayuri Shima, Yasuaki Mizutani, Akihiro Ueda, Mizuki Ito; J Mov Disord. 2023;16(1):13-21. Published online December 20, 2022; DOI: https://doi.org/10.14802/jmd.22082; Funded: Research Committee of Ataxia, Health Labour Sciences Research Grant, Ministry of Health, Labour and Welfare

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Abstract PDF: This review summarizes improvements in understanding the pathophysiology and early clinical symptoms of multiple system atrophy (MSA) and advancements in diagnostic methods and disease-modifying therapies for the condition. In 2022, the Movement Disorder Society proposed new diagnostic criteria to develop disease-modifying therapies and promote clinical trials of MSA since the second consensus was proposed in 2008. Regarding pathogenesis, cutting-edge findings have accumulated on the interactions of α-synuclein, neuroinflammation, and oligodendroglia with neurons. In neuroimaging, introducing artificial intelligence, machine learning, and deep learning has notably improved diagnostic accuracy and individual analyses. Advancements in treatment have also been achieved, including immunotherapy therapy against α-synuclein and serotonin-targeted and mesenchymal stem cell therapies, which are thought to affect several aspects of the disease, including neuroinflammation. The accelerated progress in clarifying the pathogenesis of MSA over the past few years and the development of diagnostic techniques for detecting early-stage MSA are expected to facilitate the development of disease-modifying therapies for one of the most intractable neurodegenerative diseases.

Original Article

Association of Depression With Early Occurrence of Postural Instability in Parkinson’s Disease: Yun Su Hwang, Sungyang Jo, Kye Won Park, Seung Hyun Lee, Sangjin Lee, Sun Ju Chung; J Mov Disord. 2023;16(1):68-78. Published online December 20, 2022; DOI: https://doi.org/10.14802/jmd.22091; Funded: Asan Institute for Life Sciences, Asan Medical Center

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Abstract PDF Supplementary Material: Objective
Depression in Parkinson’s disease (PD) affects the quality of life of patients. Postural instability and gait disturbance are associated with the severity and prognosis of PD. We investigated the association of depression with axial involvement in early-stage PD patients.
Methods
This study involved 95 PD patients unexposed to antiparkinsonian drugs. After a baseline assessment for depression, the subjects were divided into a depressed PD group and a nondepressed PD group. Analyses were conducted to identify an association of depression at baseline with the following outcome variables: the progression to Hoehn and Yahr scale (H-Y) stage 3, the occurrence of freezing of gait (FOG), levodopa-induced dyskinesia, and wearing-off. The follow-up period was 53.40 ± 16.79 months from baseline.
Results
Kaplan–Meier survival curves for H-Y stage 3 and FOG showed more prominent progression to H-Y stage 3 and occurrences of FOG in the depressed PD group than in the nondepressed PD group (log-rank p = 0.025 and 0.003, respectively). Depression in drug-naïve, early-stage PD patients showed a significant association with the progression to H-Y stage 3 (hazard ratio = 2.55; 95% confidence interval = 1.32–4.93; p = 0.005), as analyzed by Cox regression analyses. In contrast, the occurrence of levodopa-induced dyskinesia and wearing-off did not differ between the two groups (log-rank p = 0.903 and 0.351, respectively).
Conclusion
Depression in drug-naïve, early-stage PD patients is associated with an earlier occurrence of postural instability. This suggests shared nondopaminergic pathogenic mechanisms and potentially enables the prediction of early development of postural instability.

Case Report

A KMT2B Frameshift Variant Causing Focal Dystonia Restricted to the Oromandibular Region After Long-Term Follow-up: Alfand Marl F. Dy Closas, Katja Lohmann, Ai Huey Tan, Norlinah Mohamed Ibrahim, Jia Lun Lim, Yi Wen Tay, Kalai Arasu Muthusamy, Azlina Binti Ahmad-Annuar, Christine Klein, Shen-Yang Lim; J Mov Disord. 2023;16(1):91-94. Published online December 20, 2022; DOI: https://doi.org/10.14802/jmd.22109; Funded: Ministry of Higher Education, Malaysia, University of Malaya Parkinson’s Disease, Movement Disorders Research Program, German Research Foundation

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Abstract PDF Supplementary Material: KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.

Brief communication

Validity and Reliability of the Korean-Translated Version of the International Cooperative Ataxia Rating Scale in Cerebellar Ataxia: Jinse Park, Jin Whan Cho, Jinyoung Youn, Engseok Oh, Wooyoung Jang, Joong-Seok Kim, Yoon-Sang Oh, Hyungyoung Hwang, Chang-Hwan Ryu, Jin-Young Ahn, Jee-Young Lee, Seong-Beom Koh, Jae H. Park, Hee-Tae Kim; J Mov Disord. 2023;16(1):86-90. Published online December 20, 2022; DOI: https://doi.org/10.14802/jmd.22137; Funded: Corestem Inc

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Abstract PDF Supplementary Material: Objective
The International Cooperative Ataxia Rating Scale (ICARS) is a semiquantitative clinical scale for ataxia that is widely used in numerous countries. The purpose of this study was to investigate the validity and reliability of the Korean-translated version of the ICARS.
Methods
Eighty-eight patients who presented with cerebellar ataxia were enrolled. We investigated the construct validity using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). We also investigated the internal consistency using Cronbach’s α and intrarater and interrater reliability using intraclass correlation coefficients.
Results
The Korean-translated ICARS showed satisfactory construct validity using EFA and CFA. It also revealed good interrater and intrarater reliability and showed acceptable internal consistency. However, subscale 4 for assessing oculomotor disorder showed moderate internal consistency.
Conclusion
This is the first report to investigate the validity and reliability of the Korean-translated ICARS. Our results showed excellent construct and convergent validity. The reliability is also acceptable.

Letter to the editor

Myoclonus-Dystonic Presentation of Childhood Onset DYT-GCH1: A Report From India: Praveen Sharma, Vikram V Holla, Sandeep Gurram, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal; J Mov Disord. 2023;16(1):101-103. Published online January 12, 2023; DOI: https://doi.org/10.14802/jmd.22106; Funded: Parkinson’s Disease and Movement Disorders Research Fund, Indian Council of Medical Research

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Review Article

Current Status and Future Perspectives on Stem Cell-Based Therapies for Parkinson’s Disease: Young Cha, Tae-Yoon Park, Pierre Leblanc, Kwang-Soo Kim; J Mov Disord. 2023;16(1):22-41. Published online January 12, 2023; DOI: https://doi.org/10.14802/jmd.22141; Funded: National Institutes of Health, Parkinson’s Cell Therapy Research Fund, McLean Hospital, Massachusetts General Hospital, Masson Family Endowed Scholar in Neurosurgery, Massachusetts General Hospital

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Abstract PDF: Parkinson’s disease (PD) is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1%–2% of the population over the age of 65. As the population ages, it is anticipated that the burden on society will significantly escalate. Although symptom reduction by currently available pharmacological and/or surgical treatments improves the quality of life of many PD patients, there are no treatments that can slow down, halt, or reverse disease progression. Because the loss of a specific cell type, midbrain dopamine neurons in the substantia nigra, is the main cause of motor dysfunction in PD, it is considered a promising target for cell replacement therapy. Indeed, numerous preclinical and clinical studies using fetal cell transplantation have provided proof of concept that cell replacement therapy may be a viable therapeutic approach for PD. However, the use of human fetal cells remains fraught with controversy due to fundamental ethical, practical, and clinical limitations. Groundbreaking work on human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, coupled with extensive basic research in the stem cell field offers promising potential for hPSC-based cell replacement to become a realistic treatment regimen for PD once several major issues can be successfully addressed. In this review, we will discuss the prospects and challenges of hPSC-based cell therapy for PD.

Letter to the editor

First Cases of Spinocerebellar Ataxia 42 in Two Korean Families: Hyoshin Son, Jihoon G. Yoon, Man Jin Kim, Jangsup Moon, Han-Joon Kim; J Mov Disord. 2023;16(1):110-113. Published online January 12, 2023; DOI: https://doi.org/10.14802/jmd.22150; Funded: Research of Korea Centers for Disease Control and Prevention

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Original Article

The Effect of Blood Lipids, Type 2 Diabetes, and Body Mass Index on Parkinson’s Disease: A Korean Mendelian Randomization Study: Kye Won Park, Yun Su Hwang, Seung Hyun Lee, Sungyang Jo, Sun Ju Chung; J Mov Disord. 2023;16(1):79-85. Published online January 12, 2023; DOI: https://doi.org/10.14802/jmd.22175; Funded: Korea Movement Disorder Society

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Abstract PDF Supplementary Material: Objective
Associations between various metabolic conditions and Parkinson’s disease (PD) have been previously identified in epidemiological studies. We aimed to investigate the causal effect of lipid levels, type 2 diabetes mellitus (T2DM), and body mass index (BMI) on PD in a Korean population via Mendelian randomization (MR).
Methods
Two-sample MR analyses were performed with inverse-variance weighted (IVW), weighted median, and MR-Egger regression approaches. We identified genetic variants associated with lipid concentrations, T2DM, and BMI in publicly available summary statistics, which were either collected from genome-wide association studies (GWASs) or from meta-analyses of GWAS that targeted only Korean individuals or East Asian individuals, including Korean individuals. The outcome dataset was a GWAS on PD performed in a Korean population.
Results
From previous GWASs and meta-analyses, we selected single nucleotide polymorphisms as the instrumental variables. Variants associated with serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, as well as with T2DM and BMI, were selected (n = 11, 19, 17, 89, and 9, respectively). There were no statistically significant causal associations observed between the five exposures and PD using either the IVW, weighted median, or MR-Egger methods (p-values of the IVW method: 0.332, 0.610, 0.634, 0.275, and 0.860, respectively).
Conclusion
This study does not support a clinically relevant causal effect of lipid levels, T2DM, and BMI on PD risk in a Korean population.

Letter to the editor

Refractory Myoclonus as a Presentation of Metabolic Stroke in A Child With Cobalamin B Methylmalonic Acidemia After Liver and Kidney Transplant: Valerie Olson, Irene J Chang, J Lawrence Merritt nd, Dararat Mingbunjerdsuk; J Mov Disord. 2022;15(3):281-283. Published online May 26, 2022; DOI: https://doi.org/10.14802/jmd.21196; Funded: Veterans Affairs Advanced Fellowship Program in Parkinson’s Disease

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Citations

Citations to this article as recorded by

Neurologic outcome following liver transplantation for methylmalonic aciduria
Diego Martinelli, Giulio Catesini, Benedetta Greco, Alessia Guarnera, Chiara Parrillo, Evelina Maines, Daniela Longo, Antonio Napolitano, Francesca De Nictolis, Sara Cairoli, Daniela Liccardo, Stefania Caviglia, Anna Sidorina, Giorgia Olivieri, Barbara Si
Journal of Inherited Metabolic Disease.2023;[Epub] CrossRef

Original Articles

Semiautomated Algorithm for the Diagnosis of Multiple System Atrophy With Predominant Parkinsonism: Woong-Woo Lee, Han-Joon Kim, Hong Ji Lee, Han Byul Kim, Kwang Suk Park, Chul-Ho Sohn, Beomseok Jeon; J Mov Disord. 2022;15(3):232-240. Published online July 26, 2022; DOI: https://doi.org/10.14802/jmd.21178; Funded: National Research Foundation of Korea, Ministry of Science and ICT

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Abstract PDF Supplementary Material: Objective
Putaminal iron deposition is an important feature that helps differentiate multiple system atrophy with predominant parkinsonism (MSA-p) from Parkinson’s disease (PD). Most previous studies used visual inspection or quantitative methods with manual manipulation to perform this differentiation. We investigated the value of a new semiautomated diagnostic algorithm using 3T-MR susceptibility-weighted imaging for MSA-p.
Methods
This study included 26 MSA-p, 68 PD, and 41 normal control (NC) subjects. The algorithm was developed in 2 steps: 1) determine the image containing the remarkable putaminal margin and 2) calculate the phase-shift values, which reflect the iron concentration. The next step was to identify the best differentiating conditions among several combinations. The highest phaseshift value of each subject was used to assess the most effective diagnostic set.
Results
The raw phase-shift values were present along the lateral margin of the putamen in each group. It demonstrates an anterior- to-posterior gradient that was identified most frequently in MSA-p. The average of anterior 5 phase shift values were used for normalization. The highest area under the receiver operating characteristic curve (0.874, 80.8% sensitivity, and 86.7% specificity) of MSA-p versus PD was obtained under the combination of 3 or 4 vertical pixels and one dominant side when the normalization methods were applied. In the subanalysis for the MSA-p patients with a longer disease duration, the performance of the algorithm improved.
Conclusion
This algorithm detected the putaminal lateral margin well, provided insight into the iron distribution of the putaminal rim of MSA-p, and demonstrated good performance in differentiating MSA-p from PD.

Long-Term Outcomes of Deep Brain Stimulation in Pantothenate Kinase-Associated Neurodegeneration-Related Dystonia: Kyung Ah Woo, Han-Joon Kim, Seung-Ho Jeon, Hye Ran Park, Kye Won Park, Seung Hyun Lee, Sun Ju Chung, Jong-Hee Chae, Sun Ha Paek, Beomseok Jeon; J Mov Disord. 2022;15(3):241-248. Published online July 26, 2022; DOI: https://doi.org/10.14802/jmd.22002; Funded: Seoul National University Hospital, Institute of Information and Communications Technology Planning and Evaluation, Forest Hills, HLB Pharmaceutical, Ministry of Health and Welfare, Kuhnil Pharmaceutical, Peptron, Novartis Korea, Ipsen Korea, Samil Pharmaceutical, Abbvie Korea, Seoul National University Hospital, Seoul National University College of Medicine, Korean Brain Research Institute

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Abstract PDF Supplementary Material: Objective
To investigate the long-term clinical outcomes of pallidal deep brain stimulation (GPi-DBS) in patients with pantothenate kinase-associated neurodegeneration (PKAN).
Methods
We reviewed the records of patients with genetically confirmed PKAN who received bilateral GPi-DBS for refractory dystonia and were clinically followed up for at least 2 years postoperatively at two centers in Korea. Pre- and postoperative Burke– Fahn–Marsden Dystonia Rating Scale motor subscale (BFMDRS-M) scores, disability subscale (BFMDRS-D) scores, and qualitative clinical information were prospectively collected. Descriptive analysis was performed for BFMDRS-M scores, BFMDRSD scores, and the orofacial, axial, and limb subscores of the BFMDRS-M at 6–12, 24–36, and 60–72 months postoperatively.
Results
Five classic-type, four atypical-type, and one unknown-type PKAN cases were identified. The mean preoperative BFMDRS-M score was 92.1 for the classic type and 38.5 for the atypical or unknown type, with a mean BFMDRS follow-up of 50.7 months and a clinical follow-up of 69.0 months. The mean improvements in BFMDRS-M score were 11.3%, 41.3%, and 30.5% at 6–12, 24–36, and 60–72 months, respectively. In four patients with full regular evaluations until 60–72 months, improvements in the orofacial, axial, and limb subscores persisted, but the disability scores worsened from 24–36 months post-operation compared to the baseline, mainly owing to the aggravation of eating and feeding disabilities.
Conclusion
The benefits of GPi-DBS on dystonia may persist for more than 5 years in PKAN. The effects on patients’ subjective disability may have a shorter duration despite improvements in dystonia owing to the complex manifestations of PKAN.

Case Report

Nearly Abolished Dopamine Transporter Uptake in a Patient With a Novel FBXO7 Mutation: Eun Young Kim, Seon Young Kim, Youngduk Seo, Chaewon Shin; J Mov Disord. 2022;15(3):269-272. Published online July 26, 2022; DOI: https://doi.org/10.14802/jmd.22006; Funded: Chungnam National University Sejong Hospital

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Abstract PDF Supplementary Material

Mutations in the F-box only protein 7 (FBXO7) gene are the cause of autosomal recessive parkinsonian-pyramidal syndrome. Herein, we report a patient with a novel FBXO7 mutation with a unique clinical presentation. A 43-year-old male visited our hospital with complaints of progressing gait disturbance since a generalized tonic clonic seizure. There were no past neurological symptoms or familial disorders. Neurological examination revealed bradykinesia, masked face, stooped posture, parkinsonian gait, and postural instability. The bilateral uptake by dopamine transporters was nearly abolished, as determined by N-(3-[18F]fluoropropyl)- 2β-carbon ethoxy-3β-(4-iodophenyl) nortropane positron emission tomography (18F-FP-CIT PET). Next-generation sequencing revealed a heterozygous c.1066_1069delTCTG (p.Ser356ArgfsTer56) frameshift variant and a heterozygous c.80G>A (p.Arg27His) missense variant of the FBXO7 gene. The patient’s specific clinical features, medication-refractory parkinsonism and seizures further broaden the spectrum of FBXO7 mutations. The nearly abolished dopamine transporter uptake identified by 18F-FP-CIT PET is frequently found in patients with FBXO7 mutations, which is different from the usual rostrocaudal gradient that is observed in patients with Parkinson’s disease.

Citations

Citations to this article as recorded by

The characteristics of FBXO7 and its role in human diseases
Yeling Zhong, Jinyun Li, Meng Ye, Xiaofeng Jin
Gene.2023; 851: 146972. CrossRef

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