Journal of Movement Disorders

Volume 15(1); January 2022

Review Articles

Evidence of Inflammation in Parkinson’s Disease and Its Contribution to Synucleinopathy: Thuy Thi Lai, Yun Joong Kim, Hyeo-il Ma, Young Eun Kim; J Mov Disord. 2022;15(1):1-14. Published online November 3, 2021; DOI: https://doi.org/10.14802/jmd.21078

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Accumulation of alpha-synuclein (αSyn) protein in neurons is a renowned pathological hallmark of Parkinson’s disease (PD). In addition, accumulating evidence indicates that activated inflammatory responses are involved in the pathogenesis of PD. Thus, achieving a better understanding of the interaction between inflammation and synucleinopathy in relation to the PD process will facilitate the development of promising disease-modifying therapies. In this review, the evidence of inflammation in PD is discussed, and human, animal, and laboratory studies relevant to the relationship between inflammation and αSyn are explored as well as new therapeutic targets associated with this relationship.

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A2A Adenosine Receptor Antagonists: Are Triazolotriazine and Purine Scaffolds Interchangeable?
Andrea Spinaci, Catia Lambertucci, Michela Buccioni, Diego Dal Ben, Claudia Graiff, Maria Cristina Barbalace, Silvana Hrelia, Cristina Angeloni, Seyed Khosrow Tayebati, Massimo Ubaldi, Alessio Masi, Karl-Norbert Klotz, Rosaria Volpini, Gabriella Marucci
Molecules.2022; 27(8): 2386. CrossRef
Oligomeropathies, inflammation and prion protein binding
Gianluigi Forloni, Pietro La Vitola, Claudia Balducci
Frontiers in Neuroscience.2022;[Epub] CrossRef

Gene Therapy for Huntington’s Disease: The Final Strategy for a Cure?: Seulgi Byun, Mijung Lee, Manho Kim; J Mov Disord. 2022;15(1):15-20. Published online November 17, 2021; DOI: https://doi.org/10.14802/jmd.21006

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Huntington’s disease (HD) has become a target of the first clinical trials for gene therapy among movement disorders with a genetic origin. More than 100 clinical trials regarding HD have been tried, but all failed, although there were some improvements limited to symptomatic support. Compared to other neurogenetic disorders, HD is known to have a single genetic target. Thus, this is an advantage and its cure is more feasible than any other movement disorder with heterogeneous genetic causes. In this review paper, the authors attempt to cover the characteristics of HD itself while providing an overview of the gene transfer methods currently being researched, and will introduce an experimental trial with a preclinical model of HD followed by an update on the ongoing clinical trials for patients with HD.

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Mitochondrial organization and structure are compromised in fibroblasts from patients with Huntington’s disease
Marie Vanisova, Hana Stufkova, Michaela Kohoutova, Tereza Rakosnikova, Jana Krizova, Jiri Klempir, Irena Rysankova, Jan Roth, Jiri Zeman, Hana Hansikova
Ultrastructural Pathology.2022; 46(5): 462. CrossRef
Pathogenesis of Huntington’s Disease: An Emphasis on Molecular Pathways and Prevention by Natural Remedies
Zainab Irfan, Sofia Khanam, Varnita Karmakar, Sayeed Mohammed Firdous, Bothaina Samih Ismail Abou El Khier, Ilyas Khan, Muneeb U. Rehman, Andleeb Khan
Brain Sciences.2022; 12(10): 1389. CrossRef

The Supplementary Motor Complex in Parkinson’s Disease: Shervin Rahimpour, Shashank Rajkumar, Mark Hallett; J Mov Disord. 2022;15(1):21-32. Published online November 25, 2021; DOI: https://doi.org/10.14802/jmd.21075

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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both motor and nonmotor symptoms. Although the basal ganglia is traditionally the primary brain region implicated in this disease process, this limited view ignores the roles of the cortex and cerebellum that are networked with the basal ganglia to support motor and cognitive functions. In particular, recent research has highlighted dysfunction in the supplementary motor complex (SMC) in patients with PD. Using the PubMed and Google Scholar search engines, we identified research articles using keywords pertaining to the involvement of the SMC in action sequencing impairments, temporal processing disturbances, and gait impairment in patients with PD. A review of abstracts and full-text articles was used to identify relevant articles. In this review of 63 articles, we focus on the role of the SMC in PD, highlighting anatomical and functional data to create new perspectives in understanding clinical symptoms and, potentially, new therapeutic targets. The SMC has a nuanced role in the pathophysiology of PD, with both hypo- and hyperactivation associated with various symptoms. Further studies using more standardized patient populations and functional tasks are needed to more clearly elucidate the role of this region in the pathophysiology and treatment of PD.

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A new model for freedom of movement using connectomic analysis
Diego Alonzo Rodríguez-Méndez, Daniel San-Juan, Mark Hallett, Chris G. Antonopoulos, Erick López-Reynoso, Ricardo Lara-Ramírez
PeerJ.2022; 10: e13602. CrossRef

Original Articles

Association of AXIN1 With Parkinson’s Disease in a Taiwanese Population: Hwa-Shin Fang, Chih-Ying Chao, Chun-Chieh Wang, Wen-Lang Fan, Po-Jung Huang, Hon-Chung Fung, Yih-Ru Wu; J Mov Disord. 2022;15(1):33-37. Published online November 17, 2021; DOI: https://doi.org/10.14802/jmd.21073

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Abstract PDF Supplementary Material: Objective
A meta-analysis of locus-based genome-wide association studies recently identified a relationship between AXIN1 and Parkinson’s disease (PD). Few studies of Asian populations, however, have reported such a genetic association. The influences of rs13337493, rs758033, and rs2361988, three PD-associated genetic variants of AXIN1, were investigated in the present study because AXIN1 is related to Wnt/β-catenin signaling.
Methods
A total of 2,418 individuals were enrolled in our Taiwanese cohort for analysis of the genotypic and allelic frequency. Polymerase chain reaction–restriction fragment length polymorphism analysis was employed for rs13337493 genotyping, and the Agena MassARRAY platform (Agena Bioscience, San Diego, CA, USA) was used for rs758033 and rs2361988 genotyping in 672 patients with PD and 392 controls. Taiwan Biobank data of another 1,354 healthy controls were subjected to whole-genome sequencing performed using Illumina platforms at approximately 30× average depth.
Results
Our results revealed that rs758033 {odds ratios [OR] (95% confidence interval [CI]) = 0.267 [0.064, 0.795], p = 0.014} was associated with the risk of PD, and there was a trend toward a protective effect of rs2361988 (OR [95% CI] = 0.296 [0.071, 0.884], p = 0.026) under the recessive model. The TT genotype of rs758033 (OR [95% CI] = 0.271 [0.065, 0.805], p = 0.015) and the CC genotype of rs2361988 (OR [95% CI] = 0.305 [0.073, 0.913], p = 0.031) were less common in the PD group than in the non-PD group.
Conclusion
Our findings indicate that the rs758033 and rs2361988 polymorphisms of AXIN1 may affect the risk of PD in the Taiwanese population.

Constipation is Associated With Mild Cognitive Impairment in Patients With de novo Parkinson’s Disease: Sung Hoon Kang, Jungyeun Lee, Seong-Beom Koh; J Mov Disord. 2022;15(1):38-42. Published online November 17, 2021; DOI: https://doi.org/10.14802/jmd.21074

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Objective
The association between gastrointestinal (GI) symptoms and cognitive profile in patients with Parkinson’s disease (PD) at diagnosis remains unclear, although GI symptoms and cognitive impairment are highly prevalent in patients with PD. We investigated the relationship between constipation and cognitive status. We also aimed to identify the correlation between constipation and each neuropsychological dysfunction.
Methods
A total of 427 patients with de novo Parkinson’s disease with normal cognition (PD-NC, n = 170) and Parkinson’s disease with mild cognitive impairment (PD-MCI, n = 257) at Korea University Guro Hospital in Seoul, Korea were included. All patients underwent comprehensive neuropsychological tests and completed the Non-Motor Symptoms Scale (NMSS). The frequency and severity of constipation were assessed using the NMSS GI symptoms scale, we used logistic regression analysis and partial correlation analysis to determine the associations between constipation score, MCI, and each neuropsychological dysfunction.
Results
Frequent and severe constipation was associated with MCI in patients with PD at diagnosis regardless of disease severity. Specifically, constipation was related to poor performance in frontal-executive and visuospatial functions after controlling for age and sex.
Conclusion
Our findings may provide an understanding of constipation as a marker associated with cognitive impairment in individuals with PD. Therefore, the evaluation of cognitive function is warranted in PD patients with constipation, while further studies are necessary to investigate the detailed mechanism of our results.

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Interactions between gut microbiota and Parkinson's disease: The role of microbiota-derived amino acid metabolism
Wang Wang, Shujun Jiang, Chengcheng Xu, Lili Tang, Yan Liang, Yang Zhao, Guoxue Zhu
Frontiers in Aging Neuroscience.2022;[Epub] CrossRef

Premonitory Urges Reconsidered: Urge Location Corresponds to Tic Location in Patients With Primary Tic Disorders: Jana Essing, Ewgeni Jakubovski, Nikolas Psathakis, Sinan N Cevirme, James F Leckman, Kirsten R Müller-Vahl; J Mov Disord. 2022;15(1):43-52. Published online January 25, 2022; DOI: https://doi.org/10.14802/jmd.21045

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Abstract PDF Supplementary Material

Objective
In patients with Tourette syndrome and other primary tic disorders (PTDs), tics are typically preceded by premonitory urges (PUs). To date, only a few studies have investigated the location and frequency of PUs, and contrary to clinical experience, the results suggest that PUs are not located in the same anatomic region as the tics. This study aimed to further explore PU location and frequency in detail, differentiating the kind and complexity of the corresponding tics, in a large sample of patients with PTD.
Methods
A total of 291 adult (≥ 18 years) patients with a confirmed diagnosis of chronic PTD were included. The study was conducted online, assement included tics and the general characterization of PUs and a sophisticated body drawing for locating PUs.
Results
We found that PUs were located in the same body area as, or in direct proximity to, the corresponding tic. Most frequently, PUs were located in the face and at the head (62.1%). Compared with simple tics, complex (motor and vocal) tics were more often preceded by a PU; but there was no difference in PU frequency observed between motor tics and vocal tics. PUs were more often experienced at the front than at the back of the body (73% vs. 27%), while there was no difference between the right and left sides (41.6% vs. 41.3%).
Conclusion
The strong association between PU and tic location further supports the hypothesis that PUs represent the core of PTD. Accordingly, future therapies should focus on treating PUs to achieve greater tic reduction.

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Mass social media-induced illness presenting with Tourette-like behavior
Carolin Fremer, Natalia Szejko, Anna Pisarenko, Martina Haas, Luise Laudenbach, Claudia Wegener, Kirsten R. Müller-Vahl
Frontiers in Psychiatry.2022;[Epub] CrossRef

Brief communications

Dance Intervention Using the Feldenkrais Method Improves Motor, and Non-Motor Symptoms and Gait in Parkinson’s Disease: A 12-Month Study: Sung Hoon Kang, Jinhee Kim, Ilsoo Kim, Young Ae Moon, Sojung Park, Seong-Beom Koh; J Mov Disord. 2022;15(1):53-57. Published online November 3, 2021; DOI: https://doi.org/10.14802/jmd.21086

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Abstract PDF Supplementary Material

Objective
The aim of this study was to assess the effects of dancing (using the Feldenkrais method) on motor and non-motor symptoms, quality of life (QoL), and objective parameters of gait at the time of intervention and at the end of the 1-year study period.
Methods
This was a single-arm study in which 12 subjects with Parkinson’s disease (PD) received dance intervention during a 6-month period. Objective motor scales, gait analysis, and questionnaires on non-motor symptoms were evaluated at baseline and at 3, 6, and 12 months.
Results
Dance intervention decreased motor scale (Unified Parkinson’s Disease Rating Scale and Tinetti scale) scores and improved gait disturbance (gait velocity and step length) without increasing levodopa equivalent dose. Furthermore, dancing decreased non-motor scale (Non-Motor Symptoms Scale and Montgomery-Asberg Depression Rating Scale) scores and improved QoL.
Conclusion
Our findings suggest that dance intervention can be a complementary management method for PD patients.

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Mild cognitive impairment is associated with poor gait performance in patients with Parkinson’s disease
Sung Hoon Kang, Jinhee Kim, Jungyeun Lee, Seong-Beom Koh
Frontiers in Aging Neuroscience.2022;[Epub] CrossRef

Current Status of Telemedicine for Parkinson’s Disease in Japan: A Single-Center Cross-Sectional Questionnaire Survey: Mayuko Ogawa, Genko Oyama, Satoko Sekimoto, Taku Hatano, Nobutaka Hattori; J Mov Disord. 2022;15(1):58-61. Published online December 24, 2021; DOI: https://doi.org/10.14802/jmd.21096

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Abstract PDF Supplementary Material

Objective
Using telemedicine is a way to improve the accessibility of specialists for patients with Parkinson’s disease (PD); however, it is not widely used in Japan. We investigated the efficacy of telemedicine in PD by using a single-center cross-sectional questionnaire survey.
Methods
We sent a questionnaire to patients who agreed to participate from among 52 patients with PD who had used telemedicine services at Juntendo University Hospital from October 2017 to November 2018. Caregivers were asked to respond to one question separately.
Results
A total of 38 patients responded to the questionnaire. Most patients were satisfied with the telemedicine consultation (7.8 ± 1.9), reporting that it was effective in reducing their travel burden. Twenty-one patients attended a telemedicine consultation with their caregivers, and their satisfaction was high (8.4 ± 1.8).
Conclusion
In a specific cohort in Japan, patients with PD and their caregivers were mostly satisfied with the telemedicine service.

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Perspectives on Telemedicine
彦光大山, 信孝服部
Iryou kikigaku (The Japanese journal of medical instrumentation).2022; 92(3): 331. CrossRef
Effects of LSVT-BIG via telerehabilitation on non-motor and motor symptoms and quality of life in Parkinson’s disease
Yasemin Ekmekyapar Fırat, Türkan Turgay, Selver Seval Soğan, Pınar Günel Karadeniz
Acta Neurologica Belgica.2022;[Epub] CrossRef

Case Reports

Deep Brain Stimulation for Cockayne Syndrome-Associated Movement Disorder: Joseph S. Domino, Rose Gelineau-Morel, Christian Kaufman; J Mov Disord. 2022;15(1):62-65. Published online November 3, 2021; DOI: https://doi.org/10.14802/jmd.21005

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Abstract PDF Supplementary Material: Cockayne syndrome (CS) is a rare progeroid disorder characterized by multisystem degeneration, including neurological dysfunction, for which deep brain stimulation (DBS) is a proposed treatment. This study represents only the third case of DBS for CS-associated movement disorder and the first in which both proposed targets had devices implanted, allowing for direct comparison. A case of DBS for CS-associated movement disorder is presented. Previous literature documents two cases with one targeting the ventral intermediate nucleus of the thalamus (VIM) and the other targeting the globus pallidus interna (GPi). Our patient underwent stimulation of GPi nuclei followed by repositioning to VIM nuclei with improved symptom control using VIM stimulation. In all cases, there was a significant clinical benefit without off-target effects. CS-associated movement disorder exhibits phenotypic variability for which DBS is a viable treatment. Target selection should be driven by clinical phenotype.

Parainfectious Anti-Glial Fibrillary Acidic Protein-Associated Meningoencephalitis: Jae Young Joo, Dallah Yoo, Tae-Beom Ahn; J Mov Disord. 2022;15(1):66-70. Published online November 25, 2021; DOI: https://doi.org/10.14802/jmd.21115

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Movement disorders associated with glial fibrillary acidic protein (GFAP) autoantibodies have rarely been reported as ataxia or tremors. A 32-year-old man with headache and fever, initially diagnosed with viral meningoencephalitis, showed gradual improvement with empirical treatment. Two weeks after the illness, he suddenly developed orofacial, tongue, and neck dyskinesia accompanied by oculomotor abnormalities, which developed into severe generalized choreoballism. Brain magnetic resonance imaging (fluid-attenuated inversion recovery) showed signal hyperintensities in the bilateral globus pallidus interna. The clinical picture suggested an acute inflammatory trigger of secondary autoimmune encephalitis. The autoimmune antibody test was positive for GFAP, with the strongest reactivity in the cerebrospinal fluid (CSF) before treatment and decreased reactivity in serial CSF examinations during immunotherapy. Dyskinesia gradually improved to the extent that it could be controlled with only oral medications. This patient presented with parainfectious GFAP meningoencephalitis with distinctive clinical features and imaging findings.

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Comment on “Parainfectious Anti-Glial Fibrillary Acidic Protein-Associated Meningoencephalitis”
Byoung June Ahn, Kyum-Yil Kwon
Journal of Movement Disorders.2022; 15(2): 187. CrossRef
Re: Comment on “Parainfectious Anti-Glial Fibrillary Acidic Protein-Associated Meningoencephalitis”
Dallah Yoo, Tae-Beom Ahn
Journal of Movement Disorders.2022; 15(2): 189. CrossRef

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy: Jin Ho Jung, Jung Hwa Seo, Sukyoon Lee, Young Jin Heo, Donghyun Kim, Eun Joo Chung, Seong-il Oh; J Mov Disord. 2022;15(1):71-74. Published online December 24, 2021; DOI: https://doi.org/10.14802/jmd.21091

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Abstract PDF Supplementary Material: Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalopathy is rarely considered. We report a case of co-occurring SPG4 and CADASIL. A 61-year-old male presented with sudden visual impairment after a headache. He showed a spastic gait and had a family history with similar symptoms. An SPG4 gene mutation and a pathogenic variant in the NOTCH3 gene were found. This case shows that the diverse and complex clinical manifestations of patients with extensive leukoencephalopathy are related to more than one gene mutation. We also suggest the necessity for relevant genetic tests in the diagnosis of adult-onset leukoencephalopathy.

Letters to the editor

Cortical Subarachnoid Hemorrhage Presenting with Hemibody Dystonic Myoclonus: An Illustrative Case: Hyunjin Ju, Eun Ji Lee, Mina Lee, Kayeong Im, Kyum-Yil Kwon; J Mov Disord. 2022;15(1):75-76. Published online March 15, 2021; DOI: https://doi.org/10.14802/jmd.20127

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Resilience and Trauma among Patients with Parkinson’s Disease during the COVID-19 Pandemic: Roberto Erro, Sofia Cuoco, Emanuele Nigro, Raffaele Ragone, Paolo Barone; J Mov Disord. 2022;15(1):77-79. Published online April 26, 2021; DOI: https://doi.org/10.14802/jmd.20126

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Reliability and validity of the novel Italian version of the 14-item Resilience Scale (RS-14) in adults
Sofia Cuoco, Immacolata Carotenuto, Arianna Cappiello, Rossella Bisogno, Marina Picillo, Maria Teresa Pellecchia, Paolo Barone, Roberto Erro
Neurological Sciences.2022; 43(5): 3079. CrossRef

Opsoclonus-Myoclonus Syndrome as a Heralding Feature of Scrub Typhus: An Illustrative Case with a Video Vignette: Divyani Garg, Rajinder K. Dhamija; J Mov Disord. 2022;15(1):80-82. Published online May 3, 2021; DOI: https://doi.org/10.14802/jmd.20148

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Neurological facets of scrub typhus: A comprehensive narrative review
Divyani Garg, Abi Manesh
Annals of Indian Academy of Neurology.2021; 24(6): 849. CrossRef

Dancing Feet Dyskinesia in a Patient with GBA-PD: Diana A. Olszewska, Allan McCarthy, Alexandra I. Soto-Beasley, Ronald L. Walton, Owen A. Ross, Tim Lynch; J Mov Disord. 2022;15(1):83-85. Published online May 3, 2021; DOI: https://doi.org/10.14802/jmd.20169

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