Journal of Movement Disorders

Most-download articles are from the articles published in 2021 during the last three month.

Review Articles

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

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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.

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

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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.

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

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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.

Movement Disorders Associated With Radiotherapy and Surgical Procedures: Bharath Kumar Surisetti, Shweta Prasad, Vikram Venkappayya Holla, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal; J Mov Disord. 2023;16(1):42-51. Published online January 12, 2023; DOI: https://doi.org/10.14802/jmd.22092

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Abstract PDF: Occasionally, movement disorders can occur following interventional procedures including but not limited to radiotherapy, dental procedures, and cardiac, cerebral and spinal surgeries. The majority of these disorders tend to be unexpected sequelae with variable phenomenology and latency, and they can often be far more disabling than the primary disease for which the procedure was performed. Owing to poor knowledge and awareness of the problem, delays in diagnosing the condition are common, as are misdiagnoses as functional movement disorders. This narrative review discusses the phenomenology, pathophysiology, and potential treatments of various movement disorders caused by interventional procedures such as radiotherapy and neurological and non-neurological surgeries and procedures.

Treatable Ataxias: How to Find the Needle in the Haystack?: Albert Stezin, Pramod Kumar Pal; J Mov Disord. 2022;15(3):206-226. Published online September 7, 2022; DOI: https://doi.org/10.14802/jmd.22069

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Abstract PDF: Treatable ataxias are a group of ataxic disorders with specific treatments. These disorders include genetic and metabolic disorders, immune-mediated ataxic disorders, and ataxic disorders associated with infectious and parainfectious etiology, vascular causes, toxins and chemicals, and endocrinopathies. This review provides a comprehensive overview of different treatable ataxias. The major metabolic and genetic treatable ataxic disorders include ataxia with vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann-Pick disease type C, autosomal recessive cerebellar ataxia due to coenzyme Q10 deficiency, glucose transporter type 1 deficiency, and episodic ataxia type 2. The treatment of these disorders includes the replacement of deficient cofactors and vitamins, dietary modifications, and other specific treatments. Treatable ataxias with immune-mediated etiologies include gluten ataxia, anti-glutamic acid decarboxylase antibody-associated ataxia, steroid-responsive encephalopathy associated with autoimmune thyroiditis, Miller-Fisher syndrome, multiple sclerosis, and paraneoplastic cerebellar degeneration. Although dietary modification with a gluten-free diet is adequate in gluten ataxia, other autoimmune ataxias are managed by short-course steroids, plasma exchange, or immunomodulation. For autoimmune ataxias secondary to malignancy, treatment of tumor can reduce ataxic symptoms. Chronic alcohol consumption, antiepileptics, anticancer drugs, exposure to insecticides, heavy metals, and recreational drugs are potentially avoidable and treatable causes of ataxia. Infective and parainfectious causes of cerebellar ataxias include acute cerebellitis, postinfectious ataxia, Whipple’s disease, meningoencephalitis, and progressive multifocal leukoencephalopathy. These disorders are treated with steroids and antibiotics. Recognizing treatable disorders is of paramount importance when dealing with ataxias given that early treatment can prevent permanent neurological sequelae.

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

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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.

Review Article

Pallidus Stimulation for Chorea-Acanthocytosis: A Systematic Review and Meta-Analysis of Individual Data: Weibin He, Chenhui Li, Hongjuan Dong, Lingmin Shao, Bo Yin, Dianyou Li, Liguo Ye, Ping Hu, Chencheng Zhang, Wei Yi; J Mov Disord. 2022;15(3):197-205. Published online July 26, 2022; DOI: https://doi.org/10.14802/jmd.22003

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Abstract PDF Supplementary Material: A significant proportion of patients with chorea-acanthocytosis (ChAc) fail to respond to standard therapies. Recent evidence suggests that globus pallidus internus (GPi) deep brain stimulation (DBS) is a promising treatment option; however, reports are few and limited by sample sizes. We conducted a systematic literature review to evaluate the clinical outcome of GPi-DBS for ChAc. PubMed, Embase, and Cochrane Library databases were searched for relevant articles published before August 2021. The improvement of multiple motor and nonmotor symptoms was qualitatively presented. Improvements in the Unified Huntington’s Disease Rating Scale motor score (UHDRS-MS) were also analyzed during different follow-up periods. A multivariate linear regression analysis was conducted to identify potential predictors of clinical outcomes. Twenty articles, including 27 patients, were eligible. Ninety-six percent of patients with oromandibular dystonia reported significant improvement. GPi-DBS significantly improved the UHDRS-motor score at < 6 months (p < 0.001) and ≥ 6 months (p < 0.001). The UHDRS-motor score improvement rate was over 25% in 75% (15/20 cases) of patients at long-term follow-up (≥ 6 months). The multiple linear regression analysis showed that sex, age at onset, course of disease, and preoperative movement score had no linear relationship with motor improvement at long-term follow-up (p > 0.05). GPi-DBS is an effective and safe treatment in most patients with ChAc, but no reliable predictor of efficacy has been found. Oromandibular dystonia-dominant patients might be the best candidates for GPi-DBS.

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

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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.

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

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Review Article

Immune-Mediated Cerebellar Ataxias: Clinical Diagnosis and Treatment Based on Immunological and Physiological Mechanisms: Hiroshi Mitoma, Mario Manto, Marios Hadjivassiliou; J Mov Disord. 2021;14(1):10-28. Published online January 12, 2021; DOI: https://doi.org/10.14802/jmd.20040

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20 Citations

Abstract PDF

Since the first description of immune-mediated cerebellar ataxias (IMCAs) by Charcot in 1868, several milestones have been reached in our understanding of this group of neurological disorders. IMCAs have diverse etiologies, such as gluten ataxia, postinfectious cerebellitis, paraneoplastic cerebellar degeneration, opsoclonus myoclonus syndrome, anti-GAD ataxia, and primary autoimmune cerebellar ataxia. The cerebellum, a vulnerable autoimmune target of the nervous system, has remarkable capacities (collectively known as the cerebellar reserve, closely linked to plasticity) to compensate and restore function following various pathological insults. Therefore, good prognosis is expected when immune-mediated therapeutic interventions are delivered during early stages when the cerebellar reserve can be preserved. However, some types of IMCAs show poor responses to immunotherapies, even if such therapies are introduced at an early stage. Thus, further research is needed to enhance our understanding of the autoimmune mechanisms underlying IMCAs, as such research could potentially lead to the development of more effective immunotherapies. We underscore the need to pursue the identification of robust biomarkers.

Citations

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Cell-Autonomous Processes That Impair Xenograft Survival into the Cerebellum
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Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders
Pei-Chen Hsieh, Yih-Ru Wu
Journal of Movement Disorders.2022; 15(2): 95. CrossRef
Autoimmune cerebellar ataxia associated with anti-leucine-rich glioma-inactivated protein 1 antibodies: Two pediatric cases
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Central Positional Nystagmus
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Paraneoplastic Ataxia: Antibodies at the Forefront Have Become Routine Biomarkers
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Rare Etiologies in Immune-Mediated Cerebellar Ataxias: Diagnostic Challenges
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Jiao Li, Bo Deng, Wenli Song, Keru Li, Jingwen Ai, Xiaoni Liu, Haocheng Zhang, Yi Zhang, Ke Lin, Guofu Shao, Chunfeng Liu, Wenhong Zhang, Xiangjun Chen, Yanlin Zhang
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Stiff-Eye Syndrome—Anti-GAD Ataxia Presenting with Isolated Ophthalmoplegia: A Case Report
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Original Articles

Increased Mortality in Young-Onset Parkinson’s Disease: Eldbjørg Hustad, Tor Åge Myklebust, Sasha Gulati, Jan O. Aasly; J Mov Disord. 2021;14(3):214-220. Published online July 29, 2021; DOI: https://doi.org/10.14802/jmd.21029

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Abstract PDF

Objective
Few studies have followed Parkinson’s disease (PD) patients from the time of diagnosis to the date of death. This study compared mortality in the Trondheim PD cohort to the general population, investigated causes of death and analyzed the associations between mortality and age at disease onset (AAO) and cognitive decline defined as Montreal Cognitive Assessment (MoCA) score below 26.
Methods
The cohort was followed longitudinally from 1997. By the end of January 2020, 587 patients had died. Comparisons to the Norwegian population were performed by calculating standardized mortality ratios (SMRs). Survival curves were estimated using the standard Kaplan-Meier estimator, and multivariable Cox proportional hazard models were estimated to investigate associations.
Results
SMR was 2.28 [95% confidence interval (CI): 2.13–2.44] for the whole cohort. For participants with AAO 20–39 years, the SMR was 5.55 (95% CI: 3.38–8.61). Median survival was 15 years (95% CI: 14.2–15.5) for the whole cohort. Early-onset PD (EOPD) patients (AAO < 50 years) had the longest median survival time. For all groups, there was a significant shortening in median survival time and an almost 3-fold higher age- and sex-adjusted hazard ratio for death when the MoCA score decreased below 26.
Conclusion
PD patients with an AAO before 40 years had a more than fivefold higher mortality rate compared to a similar general population. EOPD patients had the longest median survival; however, their life expectancy was reduced to a greater degree than that of late-onset PD patients. Cognitive impairment was strongly associated with mortality in PD.

Citations

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Tinetti balance performance is associated with mortality in older adults with late-onset Parkinson’s disease: a longitudinal study
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Age Cutoff for Early‐Onset Parkinson's Disease: Recommendations from the International Parkinson and Movement Disorder Society Task Force on Early Onset Parkinson's Disease
Raja Mehanna, Katarzyna Smilowska, Jori Fleisher, Bart Post, Taku Hatano, Maria Elisa Pimentel Piemonte, Kishore Raj Kumar, Victor McConvey, Baorong Zhang, Eng‐King Tan, Rodolfo Savica, Rodolfo Savica, Eng‐King Tan, Raja Mehanna, Katarzyna Smilowska, Conn
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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

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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.

Letter to the editor

Orthostatic Myoclonus as a Presentation of Hashimoto Encephalopathy: Hyunyoung Hwang, Jinse Park, Jeong Ik Eun, Kyong Jin Shin, Jongmok Ha, Jinyoung Youn; J Mov Disord. 2023;16(1):104-106. Published online January 12, 2023; DOI: https://doi.org/10.14802/jmd.22146

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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

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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.

Review Article

Diagnosis and Clinical Features in Autoimmune-Mediated Movement Disorders: Pei-Chen Hsieh, Yih-Ru Wu; J Mov Disord. 2022;15(2):95-105. Published online May 26, 2022; DOI: https://doi.org/10.14802/jmd.21077

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Abstract PDF Supplementary Material: Movement disorders are common manifestations in autoimmune-mediated encephalitis. This group of diseases is suspected to be triggered by infection or neoplasm. Certain phenotypes correlate with specific autoantibody-related neurological disorders, such as orofacial-lingual dyskinesia with N-methyl-D-aspartate receptor encephalitis and faciobrachial dystonic seizures with leucine-rich glioma-inactivated protein 1 encephalitis. Early diagnosis and treatment, especially for autoantibodies targeting neuronal surface antigens, can improve prognosis. In contrast, the presence of autoantibodies against intracellular neuronal agents warrants screening for underlying malignancy. However, early clinical diagnosis is challenging because these diseases can be misdiagnosed. In this article, we review the distinctive clinical phenotypes, magnetic resonance imaging findings, and current treatment options for autoimmune-mediated encephalitis.

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