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Volume 16(2); May 2023
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Review Articles
Adult-Onset Genetic Leukoencephalopathies With Movement Disorders
Mu-Hui Fu, Yung-Yee Chang
J Mov Disord. 2023;16(2):115-132.   Published online March 7, 2023
DOI: https://doi.org/10.14802/jmd.22127
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AbstractAbstract PDF
Genetic leukoencephalopathies (GLEs) are a group of white matter abnormalities with heterogeneous radiological and phenotypic features. Although these conditions have mostly been described in children, adult-onset cases are increasingly recognized owing to the widespread use of neuroimaging and advances in molecular genetic testing. The disease course is often progressive with a varied spectrum of presentations, trapping neurologists in the dilemma of differential diagnosis. Movement disorders are among the most common symptoms, and their diversity makes diagnosis challenging. In this review, we focus on adult-onset GLEs with movement disorders and offer a step-by-step diagnostic approach by clarifying the phenomenology of movement, advising investigations for acquired causes, describing the clinical and radiological clues to each disease, emphasizing the limitations of advanced molecular testing, and discussing the future application of artificial intelligence. We provide a list summarizing the leukoencephalopathies associated with different categories of movement disorders. In addition to guiding clinicians on how to narrow the list of differential diagnoses with the tools currently available, another aim of this review is to emphasize the inevitable trend toward applying advanced technology in diagnosing these difficult diseases.
A Brief History of NBIA Gene Discovery
Susan J. Hayflick
J Mov Disord. 2023;16(2):133-137.   Published online April 26, 2023
DOI: https://doi.org/10.14802/jmd.23014
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AbstractAbstract PDF
Neurodegenerative disorders associated with high basal ganglia iron are known by the overarching term of ‘NBIA’ disorders or ‘neurodegeneration with brain iron accumulation’. Discovery of their individual genetic bases was greatly enabled by the collection of DNA and clinical data in just a few centers. With each discovery, the remaining idiopathic disorders could be further stratified by common clinical, radiographic or pathological features to enable the next hunt. This iterative process, along with strong and open collaborations, enabled the discoveries of PANK2, PLA2G6, C19orf12, FA2H, WDR45, and COASY gene mutations as underlying PKAN, PLAN, MPAN, FAHN, BPAN, and CoPAN, respectively. The era of Mendelian disease gene discovery is largely behind us, but the history of these discoveries for the NBIA disorders has not yet been told. A brief history is offered here.

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  • COASY Protein-Associated Neurodegeneration: Report from India
    Rohan R. Mahale, Raviprakash Singh, Pavankumar Katragadda, Hansashree Padmanabha
    Annals of Indian Academy of Neurology.2023; 26(5): 834.     CrossRef
Gastrointestinal Dysfunction in Parkinson’s Disease: Neuro-Gastroenterology Perspectives on a Multifaceted Problem
Ai Huey Tan, Kee Huat Chuah, Yuan Ye Beh, Jie Ping Schee, Sanjiv Mahadeva, Shen-Yang Lim
J Mov Disord. 2023;16(2):138-151.   Published online May 24, 2023
DOI: https://doi.org/10.14802/jmd.22220
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AbstractAbstract PDF
Patients with Parkinson’s disease (PD) face a multitude of gastrointestinal (GI) symptoms, including nausea, bloating, reduced bowel movements, and difficulties with defecation. These symptoms are common and may accumulate during the course of PD but are often under-recognized and challenging to manage. Objective testing can be burdensome to patients and does not correlate well with symptoms. Effective treatment options are limited. Evidence is often based on studies in the general population, and specific evidence in PD is scarce. Upper GI dysfunction may also interfere with the pharmacological treatment of PD motor symptoms, which poses significant management challenges. Several new less invasive assessment tools and novel treatment options have emerged in recent years. The current review provides an overview and a practical approach to recognizing and diagnosing common upper and lower GI problems in PD, e.g., dyspepsia, gastroparesis, small bowel dysfunction, chronic constipation, and defecatory dysfunction. Management aspects are discussed based on the latest evidence from the PD and general populations, with insights for future research pertaining to GI dysfunction in PD.

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  • Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
    Jingyu Zhu, Wei Meng, Liang Liu, Peixin Hu, Yuling Liang, Wenwen Zhu, Xiaoyan Zhu
    Open Life Sciences.2024;[Epub]     CrossRef
Viewpoints
Diagnosis Versus Classification of Essential Tremor: A Research Perspective
Roberto Erro, Marina Picillo, Maria Teresa Pellecchia, Paolo Barone
J Mov Disord. 2023;16(2):152-157.   Published online May 24, 2023
DOI: https://doi.org/10.14802/jmd.23020
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  • Comparing Essential Tremor with and without Soft Dystonic Signs and Tremor Combined with Dystonia: The TITAN Study
    Roberto Erro, Giulia Lazzeri, Carmen Terranova, Giulia Paparella, Angelo Fabio Gigante, Rosa De Micco, Luca Magistrelli, Francesca Di Biasio, Francesca Valentino, Vincenzo Moschella, Andrea Pilotto, Marcello Esposito, Enrica Olivola, Maria Chiara Malaguti
    Movement Disorders Clinical Practice.2024;[Epub]     CrossRef
  • Clinical correlates of “pure” essential tremor: the TITAN study
    Roberto Erro, Giulia Lazzeri, Angelo Fabio Gigante, Andrea Pilotto, Luca Magistrelli, Matteo Bologna, Carmen Terranova, Enrica Olivola, Carlo Dallocchio, Vincenzo Moschella, Francesca Valentino, Francesca Di Biasio, Alessandra Nicoletti, Rosa De Micco, Li
    Frontiers in Neurology.2023;[Epub]     CrossRef
Potential Benefits and Perils of Incorporating ChatGPT to the Movement Disorders Clinic
Andres Deik
J Mov Disord. 2023;16(2):158-162.   Published online May 24, 2023
DOI: https://doi.org/10.14802/jmd.23072
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  • 4 Web of Science
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  • (How) ChatGPT—Artificial Intelligence Thinks It Can Help/Harm Physiatry
    Jakub Jačisko, Viktor Veselý, Ke-Vin Chang, Levent Özçakar
    American Journal of Physical Medicine & Rehabilitation.2024; 103(4): 346.     CrossRef
  • Patient-Friendly Discharge Summaries in Korea Based on ChatGPT: Software Development and Validation
    Hanjae Kim, Hee Min Jin, Yoon Bin Jung, Seng Chan You
    Journal of Korean Medical Science.2024;[Epub]     CrossRef
  • A Survey of Clinicians' Views of the Utility of Large Language Models
    Matthew Spotnitz, Betina Idnay, Emily R. Gordon, Rebecca Shyu, Gongbo Zhang, Cong Liu, James J. Cimino, Chunhua Weng
    Applied Clinical Informatics.2024; 15(02): 306.     CrossRef
  • Can ChatGPT diagnose my collapsing dog?
    Samira Abani, Steven De Decker, Andrea Tipold, Jasmin Nicole Nessler, Holger Andreas Volk
    Frontiers in Veterinary Science.2023;[Epub]     CrossRef
  • Bias and Inaccuracy in AI Chatbot Ophthalmologist Recommendations
    Michael C Oca, Leo Meller, Katherine Wilson, Alomi O Parikh, Allison McCoy, Jessica Chang, Rasika Sudharshan, Shreya Gupta, Sandy Zhang-Nunes
    Cureus.2023;[Epub]     CrossRef
Original Articles
The Clinical Characterization of Blocking Tics in Patients With Tourette Syndrome
José Fidel Baizabal-Carvallo, Joseph Jankovic
J Mov Disord. 2023;16(2):163-167.   Published online March 7, 2023
DOI: https://doi.org/10.14802/jmd.22122
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AbstractAbstract PDFSupplementary Material
Objective
Tourette syndrome (TS) is a neurodevelopmental disorder characterized by the presence of motor and phonic tics. Blocking phenomena, characterized by arrests in motor activity causing interruptions in movements or speech, have also been described in patients with TS. In this study, we aimed to characterize the frequency and features of blocking tics in patients with TS.
Methods
We studied a cohort of 201 patients with TS evaluated at our movement disorders clinic.
Results
We identified 12 (6%) patients with blocking phenomena. Phonic tic intrusion causing speech arrest was the most common (n = 8, 4%), followed by sustained isometric muscle contractions arresting body movements (n = 4, 2%). The following variables were statistically related to blocking phenomena: shoulder tics, leg tics, copropraxia, dystonic tics, simple phonic tics, and number of phonic tics per patient (all p < 0.050). In the multivariate regression, the presence of dystonic tics (p = 0.014) and a higher number of phonic tics (p = 0.022) were associated with blocking phenomena.
Conclusion
Blocking phenomena are present in approximately 6% of patients with TS, and the presence of dystonic tics and a higher frequency and number of phonic tics increase the risk for these phenomena.

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  • Tics emergencies and malignant tourette syndrome: Assessment and management
    José Fidel Baizabal-Carvallo, Andrea E. Cavanna, Joseph Jankovic
    Neuroscience & Biobehavioral Reviews.2024; 159: 105609.     CrossRef
  • Oromandibular tics associated with Tourette syndrome
    José Fidel Baizabal-Carvallo, Marlene Alonso-Juarez, Joseph Jankovic
    Journal of Neurology.2023; 270(5): 2591.     CrossRef
Clinical Characteristics, Genetic Features, and Long-Term Outcome of Wilson’s Disease in a Taiwanese Population: An 11-Year Follow-Up Study
Sung-Pin Fan, Yih-Chih Kuo, Ni-Chung Lee, Yin-Hsiu Chien, Wuh-Liang Hwu, Yu-Hsuan Huang, Han-I Lin, Tai-Chung Tseng, Tung-Hung Su, Shiou-Ru Tzeng, Chien-Ting Hsu, Huey-Ling Chen, Chin-Hsien Lin, Yen-Hsuan Ni
J Mov Disord. 2023;16(2):168-179.   Published online March 6, 2023
DOI: https://doi.org/10.14802/jmd.22161
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AbstractAbstract PDFSupplementary Material
Objective
aaWilson’s disease (WD) is a rare genetic disorder of copper metabolism, and longitudinal follow-up studies are limited. We performed a retrospective analysis to determine the clinical characteristics and long-term outcomes in a large WD cohort.
Methods
aaMedical records of WD patients diagnosed from 2006–2021 at National Taiwan University Hospital were retrospectively evaluated for clinical presentations, neuroimages, genetic information, and follow-up outcomes.
Results
aaThe present study enrolled 123 WD patients (mean follow-up: 11.12 ± 7.41 years), including 74 patients (60.2%) with hepatic features and 49 patients (39.8%) with predominantly neuropsychiatric symptoms. Compared to the hepatic group, the neuropsychiatric group exhibited more Kayser-Fleischer rings (77.6% vs. 41.9%, p < 0.01), lower serum ceruloplasmin levels (4.9 ± 3.9 vs. 6.3 ± 3.9 mg/dL, p < 0.01), smaller total brain and subcortical gray matter volumes (p < 0.0001), and worse functional outcomes during follow-up (p = 0.0003). Among patients with available DNA samples (n = 59), the most common mutations were p.R778L (allelic frequency of 22.03%) followed by p.P992L (11.86%) and p.T935M (9.32%). Patients with at least one allele of p.R778L had a younger onset age (p = 0.04), lower ceruloplasmin levels (p < 0.01), lower serum copper levels (p = 0.03), higher percentage of the hepatic form (p = 0.03), and a better functional outcome during follow-up (p = 0.0012) compared to patients with other genetic variations.
Conclusion
aaThe distinct clinical characteristics and long-term outcomes of patients in our cohort support the ethnic differences regarding the mutational spectrum and clinical presentations in WD.

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  • ATP7B Gene Variant Profile İdentified by NGS in Wilson’s Disease
    Orhan Gorukmez, Taner Özgür, Ozlem Gorukmez, Ali Topak
    Fetal and Pediatric Pathology.2023; 42(6): 891.     CrossRef
Safinamide as an Adjunct to Levodopa in Asian and Caucasian Patients With Parkinson’s Disease and Motor Fluctuations: A Post Hoc Analysis of the SETTLE Study
Roongroj Bhidayasiri, Takayuki Ishida, Takanori Kamei, Ryan Edbert Husni, Ippei Suzuki, Shey Lin Wu, Jin Whan Cho
J Mov Disord. 2023;16(2):180-190.   Published online April 26, 2023
DOI: https://doi.org/10.14802/jmd.22196
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AbstractAbstract PDFSupplementary Material
Objective
Safinamide is a selective, reversible monoamine oxidase B inhibitor with demonstrated efficacy and tolerability in placebo-controlled studies and is clinically useful for patients with motor fluctuations. This study evaluated the efficacy and safety of safinamide as a levodopa adjunct therapy in Asian patients with Parkinson’s disease.
Methods
Data from 173 Asian and 371 Caucasian patients from the international Phase III SETTLE study were included in this post hoc analysis. The safinamide dose was increased from 50 mg/day to 100 mg/day if no tolerability issues occurred at week 2. The primary outcome was the change from baseline to week 24 in daily ON-time without troublesome dyskinesia (i.e., ON-time). Key secondary outcomes included changes in Unified Parkinson’s Disease Rating Scale (UPDRS) scores.
Results
Safinamide significantly increased daily ON-time relative to placebo in both groups (least-squares mean: 0.83 hours, p = 0.011 [Asians]; 1.05 hours, p < 0.0001 [Caucasians]). Motor function relative to placebo (UPDRS Part III) improved significantly in Asians (-2.65 points, p = 0.012) but not Caucasians (-1.44 points, p = 0.0576). Safinamide did not worsen Dyskinesia Rating Scale scores in either subgroup, regardless of the presence or absence of dyskinesia at baseline. Dyskinesia was largely mild for Asians and moderate for Caucasians. None of the Asian patients experienced adverse events leading to treatment discontinuation.
Conclusion
Safinamide as a levodopa adjunct is well tolerated and effective in reducing motor fluctuations in both Asian and Caucasian patients. Further studies to investigate the real-world effectiveness and safety of safinamide in Asia are warranted.

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  • The Effects of Safinamide in Chinese and Non-Chinese Patients with Parkinson’s Disease
    Carlo Cattaneo, Jaime Kulisevsky
    Advances in Therapy.2024; 41(2): 638.     CrossRef
  • Safinamide as adjunctive therapy to levodopa monotherapy for patients with Parkinson's disease with wearing-off: The Japanese observational J-SILVER study
    Noriko Nishikawa, Taku Hatano, Kenya Nishioka, Shin-Ichi Ueno, Shinji Saiki, Ryota Nakamura, Asako Yoritaka, Takashi Ogawa, Yasushi Shimo, Wataru Sako, Hideki Shimura, Yoshiaki Furukawa, Takanori Kamei, Takayuki Ishida, Nobutaka Hattori
    Journal of the Neurological Sciences.2024; : 123051.     CrossRef
Reliability and Validity of the Embouchure Dystonia Severity Rating Scale
Tobias Mantel, André Lee, Shinichi Furuya, Masanori Morise, Eckart Altenmüller, Bernhard Haslinger
J Mov Disord. 2023;16(2):191-195.   Published online May 24, 2023
DOI: https://doi.org/10.14802/jmd.22213
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AbstractAbstract PDFSupplementary Material
Objective
Embouchure dystonia (ED) is a task-specific movement disorder that leads to loss of fine motor control of the embouchure and tongue muscles in wind musicians. In contrast to musicians’ hand dystonia, no validated severity rating for ED exists, posing a major obstacle for structured assessment in scientific and clinical settings. The aim of this study is to validate an ED severity rating scale (EDSRS) allowing for a standardized estimation of symptom severity in ED.
Methods
The EDSRS was set up as a composite score of six items evaluating audio-visual disease symptoms during the performance of three standardized musical tasks (sustained notes, scales, and fourths) separately for each body side. For validation, 17 musicians with ED underwent standardized audiovisual recordings during performance. Anonymized and randomized recordings were assessed by two experts in ED (raters). Statistical analysis included metrics of consistency, reliability, and construct validity with the fluctuation of the fundamental frequency of the acoustic signal (F0) (extracted in an audio analysis of the sustained notes).
Results
The EDSRS showed high internal consistency (Cronbach’s α = 0.975−0.983, corrected item-total correlations r = 0.90−0.96), interrater reliability (intraclass correlation coefficient [ICC] for agreement/consistency = 0.94/0.96), intrarater reliability over time (ICC per rater = 0.93/0.87) and good precision (standard error of measurement = 2.19/2.65), and correlated significantly with F0 variability (r = 0.55–0.60, p = 0.011–0.023).
Conclusion
The developed EDSRS is a valid and reliable tool for the assessment of ED severity in the hands of trained expert raters. Its easy applicability makes it suitable not only for routine clinical practice but also for scientific studies.
Brief communication
Sex and Gender Influence Urinary Symptoms and Management in Multiple System Atrophy
Elke Schipani Bailey, Sara J. Hooshmand, Negin Badihian, Paola Sandroni, Eduardo E. Benarroch, James H. Bower, Phillip A. Low, Wolfgang Singer, Elizabeth A. Coon
J Mov Disord. 2023;16(2):196-201.   Published online May 24, 2023
DOI: https://doi.org/10.14802/jmd.23016
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AbstractAbstract PDF
Objective
Multiple system atrophy (MSA) is characterized by urinary dysfunction, yet the influence of sex and gender on urinary symptoms and treatment is unclear. We sought to characterize sex and gender differences in the symptomatology, evaluation, and management of urinary dysfunction in patients with MSA.
Methods
Patients with MSA evaluated at our institution were reviewed and stratified by sex.
Results
While the prevalence of urinary symptoms was similar in male and female patients, incontinence was more common in females. Despite this, males and females underwent postvoid residual (PVR) measurement at similar rates. While catheterization rates were similar when PVR was measured, males were more than twice as likely to be catheterized than females in the absence of PVR measurement.
Conclusion
Urinary symptoms are common in MSA, but their presentation differs between males and females. The difference in catheterization rates may be driven by a gender disparity in referrals for PVR, which can guide treatment.

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  • In vivo cerebral metabolic and dopaminergic characteristics in multiple system atrophy with orthostatic hypotension
    Chenxi Xue, Xiaofeng Dou, Congcong Yu, Yan Zhong, Jing Wang, Xiang Zhang, Le Xue, Daoyan Hu, Shuang Wu, Hong Zhang, Mei Tian
    European Journal of Nuclear Medicine and Molecular Imaging.2024; 51(2): 468.     CrossRef
  • Sex-related differences in the clinical presentation of multiple system atrophy
    Fabian Leys, Sabine Eschlböck, Nicole Campese, Philipp Mahlknecht, Marina Peball, Georg Goebel, Victoria Sidoroff, Florian Krismer, Roberta Granata, Stefan Kiechl, Werner Poewe, Klaus Seppi, Gregor K. Wenning, Alessandra Fanciulli
    Clinical Autonomic Research.2024;[Epub]     CrossRef
Case Report
Novel Compound Heterozygous Mutations in the SYNE1 Gene in a Taiwanese Family: A Case Report and Literature Review
Chia-Yan Kuo, Pei Shan Yu, Chih-Ying Chao, Chun-Chieh Wang, Wen-Lang Fan, Yih-Ru Wu
J Mov Disord. 2023;16(2):202-206.   Published online April 26, 2023
DOI: https://doi.org/10.14802/jmd.22105
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AbstractAbstract PDFSupplementary Material
Mutations in the synaptic nuclear envelope protein 1 (SYNE1) gene are associated with substantial clinical heterogeneity. Here, we report the first case of SYNE1 ataxia in Taiwan due to two novel truncating mutations. Our patient, a 53-year-old female, exhibited pure cerebellar ataxia with c.1922del in exon 18 and c. C3883T mutations in exon 31. Previous studies have indicated that the prevalence of SYNE1 ataxia among East Asian populations is low. In this study, we identified 27 cases of SYNE1 ataxia from 22 families in East Asia. Of the 28 patients recruited in this study (including our patient), 10 exhibited pure cerebellar ataxia, and 18 exhibited ataxia plus syndromes. We could not find an exact correlation between genotypes and phenotypes. Additionally, we established a precise molecular diagnosis in our patient’s family and extended the findings on the ethnic, phenotypic, and genotypic diversity of the SYNE1 mutational spectrum.
Letters to the editor
The Frequency of Korean Patients With Parkinson’s Disease Carrying GBA Mutations in a Subgroup With Age at Onset ≤ 55 Years Old
Jin Hwangbo, Myung Jun Lee, Sang Jin Kim, Jae‑Hyeok Lee
J Mov Disord. 2023;16(2):207-209.   Published online March 7, 2023
DOI: https://doi.org/10.14802/jmd.22191
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  • Clinicogenetic Characterization of Patients with PD and Heterozygous GBA1 Variants in an Indian Cohort
    Sneha D Kamath, Vikram V. Holla, Prashant Phulpagar, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal
    Movement Disorders.2024; 39(3): 628.     CrossRef
Periodic Jaw-Opening Myoclonus in Subacute Sclerosing Panencephalitis
Divyani Garg, Ashna Kumar, Suvasini Sharma
J Mov Disord. 2023;16(2):210-212.   Published online April 26, 2023
DOI: https://doi.org/10.14802/jmd.23015
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  • Jaw Opening Myoclonus in Subacute Sclerosing Panencephalitis: A New Phenotypic Observation
    Divyani Garg, Vanshika Kakkar, Suvasini Sharma
    Journal of Movement Disorders.2024; 17(1): 106.     CrossRef
  • Movement Disorders in Patients with Subacute Sclerosing Panencephalitis: A Systematic Review
    Divyani Garg, Sahil Patel, Charulata S. Sankhla, Vikram V. Holla, Vijayashankar Paramanandam, Prashanth L. Kukkle, Sanjay Pandey, Susanne A. Schneider, Pramod K. Pal
    Movement Disorders Clinical Practice.2024;[Epub]     CrossRef
Absence of Alpha-Synuclein Pathology in the Stomach of a Patient With Prodromal Dementia With Lewy Bodies
Chaewon Shin, Seong-Ik Kim, Sung-Hye Park, Jung Hwan Shin, Chan Young Lee, Han-Joon Kim, Hyuk-Joon Lee, Seong-Ho Kong, Yun-Suhk Suh, Han-Kwang Yang, Beomseok Jeon
J Mov Disord. 2023;16(2):213-216.   Published online April 26, 2023
DOI: https://doi.org/10.14802/jmd.22219
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PDFSupplementary Material
Myorhythmia and Other Movement Disorders in Two Patients With Coronavirus Disease 2019 Encephalopathy
Rebecca Hui Min Hoe, Fan Yang, Siew Kit Shuit, Glenn Khai Wern Yong, Ser Hon Puah, Jennifer Sye Jin Ting, Mucheli Sharavan Sadasiv, Thirugnanam Umapathi
J Mov Disord. 2023;16(2):217-220.   Published online April 26, 2023
DOI: https://doi.org/10.14802/jmd.22215
  • 1,626 View
  • 32 Download
PDFSupplementary Material

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