Journal of Movement Disorders

Review Article

A practical guide for diagnostic investigations and special considerations in patients with Huntington’s disease in Korea: Jangsup Moon, Eungseok Oh, Minkyeong Kim, Ryul Kim, Dallah Yoo, Chaewon Shin, Jee-Young Lee, Jong-Min Kim, Seong-Beom Koh, Manho Kim, Beomseok Jeon; Received November 15, 2024 Accepted December 24, 2024 Published online December 26, 2024; DOI: https://doi.org/10.14802/jmd.24232 [Accepted]

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Abstract PDF: The Korean Huntington’s Disease Society (KHDS) has recently published a practical guide for clinical approach to patients with Huntington’s disease (HD) in Korea in April issue of Journal of Movement Disorders this year.¹ This article is the second practical guide particularly focused on 1) essential points of genetic counseling for families of HD covering issues of testing minors and prenatal/preimplantation testing; and 2) premanifest HD and useful laboratory investigations for assessing disease severity and progression. The latter part of this article deals with special issues of juvenile and very late-onset HD, and common comorbidities in HD patients. 3) Finally, the management principles of HD patients are briefly explained. The contents were drafted by the guideline task force members of the KHDS. We intended to include published literature containing South Korean data in this paper. We believe this article will be a pocket guide to physicians as well as movement disorders specialists in Korea in planning diagnostic work-up for and management of HD patients and families.

Original Article

Efficacy and Safety of Taltirelin Hydrate in Patients With Ataxia Due to Spinocerebellar Degeneration: Jin Whan Cho, Jee-Young Lee, Han-Joon Kim, Joong-Seok Kim, Kun-Woo Park, Seong-Min Choi, Chul Hyoung Lyoo, Seong-Beom Koh; Received May 28, 2024 Accepted October 18, 2024 Published online October 21, 2024; DOI: https://doi.org/10.14802/jmd.24127 [Epub ahead of print]

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Abstract PDF: Objective
We conducted this study to assess the efficacy and safety of taltirelin hydrate (TH) in patients with ataxia due to spinocerebellar degeneration (SCD).
Methods
Patients were randomly assigned to either the taltirelin group (5 mg orally, twice daily) or the control group. The primary endpoint was the change in the Korean version of the Scale for the Assessment and Rating of Ataxia (K-SARA) score at 24 weeks. The secondary endpoints included changes in the K-SARA score at 4 and 12 weeks as well as the Clinical Global Impression Scale, the five-level version of the EuroQol five-dimensional questionnaire, the Tinetti balance test, and gait analysis at 4, 12, and 24 weeks.
Results
A total of 149 patients (hereditary:nonhereditary=86:63) were enrolled. There were significant differences in the change in the K-SARA score at 24 weeks from baseline between the taltirelin group and the control group (-0.51±2.79 versus 0.36±2.62, respectively; p=0.0321). For the K-SARA items, the taltirelin group had significantly lower “Stance” and “Speech disturbance” subscores than the control group (-0.04±0.89 versus 0.23±0.79 and -0.07±0.74 versus 0.18±0.67; p=0.0270 and 0.0130, respectively). However, there were no significant differences in changes in other secondary efficacy outcome measures at 24 weeks from baseline between the two treatment arms (p>0.05).
Conclusion
Clinicians might consider the use of TH in the treatment of patients with ataxia due to SCD.

Brief communication

Clinico-Genetic Profiles of Seven Patients With PINK1-Related Parkinson’s Disease: A Case Series From a Tertiary Care Centre in India and a Review of the Literature: Aravind Gunasekaran, Vikram V Holla, Prashant Phulpagar, Sneha D Kamath, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal; J Mov Disord. 2024;17(4):436-441. Published online September 19, 2024; DOI: https://doi.org/10.14802/jmd.24157

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Abstract PDF Supplementary Material: Objective
Recessive variants in the PINK1 gene are known causes of early-onset Parkinson’s disease (EOPD). To describe the clinical features and genetic profiles of patients with PINK1-related Parkinson’s disease (PARK-PINK1) mutations.
Methods
We conducted a retrospective chart review of the demographic, clinical and genetic details of patients from our database carrying biallelic PINK1 variants.
Results
A total of 7 patients whose median age at onset was 33 years (range: 20–49) were recruited. All had asymmetrical onset, tremors were present in 4 patients, abnormal posturing was present in 2 patients, and slowness was present in 1 patient. The parkinsonism phenotype was noted in 6 patients (with dystonia in four) and isolated dystonia in one. Among the 6 patients with parkinsonism, five had rest tremors, all had good levodopa responses, and four had motor fluctuations with choreiform dyskinesia. Exome sequencing revealed biallelic pathogenic/likely pathogenic variants, five of which were novel.
Conclusion
PARK-PINK1 presents as an EOPD with tremor-predominant phenotype, good levodopa-responsiveness, early motor fluctuation and dyskinesia. We describe five novel variants in PINK1 gene.

Original Article

The Impact of LRRK2 G2019S on Parkinson’s Disease: Clinical Phenotype and Treatment in Tunisian Patients: Guedi Ali Barreh, Ikram Sghaier, Youssef Abida, Alya Gharbi, Amina Nasri, Saloua Mrabet, Amira Souissi, Mouna Ben Djebara, Sameh Trabelsi, Imen Kacem, Amina Gargouri-Berrechid, Riadh Gouider; J Mov Disord. 2024;17(3):294-303. Published online April 23, 2024; DOI: https://doi.org/10.14802/jmd.23276

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Objective
LRRK2-G2019S is the most frequent mutation in North African Parkinson’s disease (PD) patients. Data on its impact on disease progression and treatment response remain elusive. Therefore, we investigated the clinical features, treatments, and complications of PD in Tunisian patients according to their LRRK2-G2019S profile.
Methods
This longitudinal retrospective study was performed in the Department of Neurology, Razi University Hospital. We included clinically diagnosed PD patients according to the Movement Disorders Society criteria and reviewed their medical records for clinical, treatment, and neuropsychological assessments. All patients were screened for the LRRK2-G2019S mutation using Sanger sequencing. The correlation between LRRK2-G2019S and clinical PD features was evaluated.
Results
We included 393 PD patients, 41.5% of whom had LRRK2-G2019S mutations. Patients with mutations were younger (p = 0.017), and female PD patients had a greater mutation frequency (p = 0.008). Mutation carriers exhibited distinct clinical features, with a greater frequency of postural instability gait difficulty forms (adjusted-p < 0.001). During disease progression, carriers showed a faster annual progression in the Unified Parkinson’s Disease Rating Scale Section III scores (adjusted-p = 0.009), and significantly higher levodopa equivalent dose values in later stages (1060.81 vs. 877.83 for 6-8 years). Motor complications, such as dyskinesia (adjusted-p < 0.001) and motor fluctuations (31.9% vs. 25.7%, adjusted-p < 0.001), were more prevalent in carriers, particularly in the later stages. LRRK2-G2019S carriers also exhibited a lower prevalence of non-motor symptoms, including episodic memory (adjusted-p < 0.001), attention (adjusted-p < 0.001), and dysexecutive disorders (adjusted-p = 0.038), as well as neuropsychiatric symptoms and dysautonomic signs.
Conclusion
The present study demonstrated that the variability of the clinical profile among Tunisian PD patients was explained by the incomplete penetrance of LRRK2-G2019S, which increased with age. Further studies using biomarker and disease progression data are necessary to improve PD management.

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Glutathione S-transferase polymorphisms (GSTM1/GSTT1) outcomes in clinical profile and treatment responsiveness among Tunisian cohort of Parkinson’s disease
Ali Barreh Guedi, Sghaier Ikram, Abida Youssef, Gharbi Alya, Souissi Amira, Mrabet Saloua, Nasri Amina, Ben Djebara Mouna, Kacem Imen, Gargouri-Berrechid Amina, Gouider Riadh
Journal of Neural Transmission.2024;[Epub] CrossRef

Case Report

Loss-of-Function Variant in the SMPD1 Gene in Progressive Supranuclear Palsy-Richardson Syndrome Patients of Chinese Ancestry: Shen-Yang Lim, Ai Huey Tan, Jia Nee Foo, Yi Jayne Tan, Elaine GY Chew, Azlina Ahmad Annuar, Alfand Marl Dy Closas, Azalea Pajo, Jia Lun Lim, Yi Wen Tay, Anis Nadhirah, Jia Wei Hor, Tzi Shin Toh, Lei Cheng Lit, Jannah Zulkefli, Su Juen Ngim, Weng Khong Lim, Huw R. Morris, Eng-King Tan, Adeline SL Ng; J Mov Disord. 2024;17(2):213-217. Published online January 31, 2024; DOI: https://doi.org/10.14802/jmd.24009

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Abstract PDF Supplementary Material

Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

Citations

Citations to this article as recorded by

Parkinson’s Disease is Predominantly a Genetic Disease
Shen-Yang Lim, Christine Klein
Journal of Parkinson’s Disease.2024; 14(3): 467. CrossRef
Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia
Adeline Su Lyn Ng, Ai Huey Tan, Yi Jayne Tan, Jia Lun Lim, Michelle Mulan Lian, Alfand Marl Dy Closas, Azlina Ahmad‐Annuar, Shanthi Viswanathan, Yuen Kang Chia, Jia Nee Foo, Weng Khong Lim, Eng‐King Tan, Shen‐Yang Lim
Movement Disorders.2024; 39(10): 1829. CrossRef
Genetic-based diagnostics of Parkinson’s disease and other Parkinsonian syndromes
Emma N. Somerville, Ziv Gan-Or
Expert Review of Molecular Diagnostics.2024; 24(12): 1111. CrossRef

Review Article

Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution: Priya Jagota, Yoshikazu Ugawa, Zakiyah Aldaajani, Norlinah Mohamed Ibrahim, Hiroyuki Ishiura, Yoshiko Nomura, Shoji Tsuji, Cid Diesta, Nobutaka Hattori, Osamu Onodera, Saeed Bohlega, Amir Al-Din, Shen-Yang Lim, Jee-Young Lee, Beomseok Jeon, Pramod Kumar Pal, Huifang Shang, Shinsuke Fujioka, Prashanth Lingappa Kukkle, Onanong Phokaewvarangkul, Chin-Hsien Lin, Cholpon Shambetova, Roongroj Bhidayasiri; J Mov Disord. 2023;16(3):231-247. Published online June 13, 2023; DOI: https://doi.org/10.14802/jmd.23065

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Abstract PDF Supplementary Material

Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.

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Genetic heterogeneity of early onset Parkinson disease: The dilemma of clinico-genetic correlation
Roopa Rajan, Vikram V. Holla, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal
Parkinsonism & Related Disorders.2024; 129: 107146. CrossRef

Original Articles

KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort: Debjyoti Dhar, Vikram V Holla, Riyanka Kumari, Neeharika Sriram, Jitender Saini, Ravi Yadav, Akhilesh Pandey, Nitish Kamble, Babylakshmi Muthusamy, Pramod Kumar Pal; J Mov Disord. 2023;16(3):285-294. Published online June 13, 2023; DOI: https://doi.org/10.14802/jmd.23035

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Objective
aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations.
Methods
aaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent.
Results
aaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes.
Conclusion
aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.

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Genetic Landscape of Dystonia in Asian Indians
Arti Saini, Inder Singh, Mukesh Kumar, Divya Madathiparambil Radhakrishnan, Ayush Agarwal, Divyani Garg, Arunmozhimaran Elavarasi, Rahul Singh, Vivek Chouhan, Sandeep, Anu Gupta, Venugopalan Yamuna Vishnu, Mamta Bhushan Singh, Rohit Bhatia, Ajay Garg, Ne
Movement Disorders Clinical Practice.2025;[Epub] CrossRef
Clinical and genetic profile of patients with dystonia: An experience from a tertiary neurology center from India
Debjyoti Dhar, Vikram V. Holla, Riyanka Kumari, Ravi Yadav, Nitish Kamble, Babylakshmi Muthusamy, Pramod Kumar Pal
Parkinsonism & Related Disorders.2024; 120: 105986. CrossRef
The clinical spectrum and pathogenesis associated with KMT2B variants in Chinese pediatric patients
Shuangjin Ding, Gang Xie, Zonglin Han, Yangming Wang, Ming Shi, Feng Zhai, Tinghong Liu, Zihang Xie, Weihua Zhang, Yun Wu, Xinying Yang, Anna Zhou, Fang Fang, Shuhong Ren, Shuli Liang, Huiqing Cao, Hui Xiong, Changhong Ding, Lifang Dai
Parkinsonism & Related Disorders.2024; 129: 107172. 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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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.

Citations

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Topographical metal burden correlates with brain atrophy and clinical severity in Wilson's disease
Sung-Pin Fan, Ya-Fang Chen, Cheng-Hsuan Li, Yih-Chih Kuo, Ni-Chung Lee, Yin-Hsiu Chien, Wuh-Liang Hwu, Tai-Chung Tseng, Tung-Hung Su, Chien-Ting Hsu, Huey-Ling Chen, Chin-Hsien Lin, Yen-Hsuan Ni
NeuroImage.2024; 299: 120829. CrossRef
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

Review Article

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.

Citations

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Genetic Testing of Movements Disorders: A Review of Clinical Utility
Dennis Yeow, Laura I. Rudaks, Sue-Faye Siow, Ryan L. Davis, Kishore R. Kumar
Tremor and Other Hyperkinetic Movements.2024;[Epub] CrossRef
Genetically Proven Ataxia With Vitamin E Deficiency With Predominant Cervicobrachial Dystonic Presentation: A Case Report From India
Vikram V. Holla, Sandeep Gurram, Sneha D. Kamath, Gautham Arunachal, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal
Journal of Movement Disorders.2024; 17(2): 220. CrossRef
Rehabilitation in Ataxia
Anupam Gupta, Navin B. Prakash, Hafis Rahman
Indian Journal of Physical Medicine and Rehabilitation.2023; 33(1): 21. CrossRef

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

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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.

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Imaging Procedure and Clinical Studies of [18F]FP-CIT PET
Changhwan Sung, Seung Jun Oh, Jae Seung Kim
Nuclear Medicine and Molecular Imaging.2024; 58(4): 185. CrossRef
Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co‐regulate proteasomes and mitochondria
Sara Al Rawi, Lorna Simpson, Guðrún Agnarsdóttir, Neil Q. McDonald, Veronika Chernuha, Orly Elpeleg, Massimo Zeviani, Roger A. Barker, Ronen Spiegel, Heike Laman
The FEBS Journal.2024; 291(12): 2565. CrossRef
The characteristics of FBXO7 and its role in human diseases
Yeling Zhong, Jinyun Li, Meng Ye, Xiaofeng Jin
Gene.2023; 851: 146972. CrossRef

Original Article

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

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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.

Citations

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Deep Brain Stimulation for Refractory Status Dystonicus in Children: Multicenter Case Series and Systematic Review
Lindsey M. Vogt, Han Yan, Brendan Santyr, Sara Breitbart, Melanie Anderson, Jürgen Germann, Karlo J. Lizarraga, Angela L. Hewitt, Alfonso Fasano, George M. Ibrahim, Carolina Gorodetsky
Annals of Neurology.2024; 95(1): 156. CrossRef
Illustration of the long-term efficacy of pallidal deep brain stimulation in a patient with PKAN dystonia
Luigi M. Romito, Fabiana Colucci, Giovanna Zorzi, Barbara Garavaglia, Ahmet Kaymak, Alberto Mazzoni, Celeste Panteghini, Nico Golfrè Andreasi, Sara Rinaldo, Vincenzo Levi, Miryam Carecchio, Roberto Eleopra
Parkinsonism & Related Disorders.2024; 123: 106977. CrossRef
Case of Hallervorden–Spatz Syndrome: A Tale of Twin Sisters
Naveen Reddy, Jitender Sharma, Anmol Sharma
Neurology India.2024; 72(2): 411. CrossRef
Patient Selection for Deep Brain Stimulation for Pantothenate Kinase-Associated Neurodegeneration
Jason L. Chan, Ashley E. Rawls, Joshua K. Wong, Penelope Hogarth, Justin D. Hilliard, Michael S. Okun
Tremor and Other Hyperkinetic Movements.2024;[Epub] CrossRef
Imaging Findings of Intracerebral Infection after Deep Brain Stimulation: Pediatric Case Series and Literature Review
Andrew Z. Yang, Alexandre Boutet, Vivek Pai, Michael J. Colditz, Artur Vetkas, Brendan Santyr, Nardin Samuel, Jurgen Germann, Sara Breitbart, Lior Elkam, Birgit Ertl‐Wagner, Alfonso Fasano, Andres M. Lozano, George M Ibrahim, Carolina Gorodetsky
Movement Disorders Clinical Practice.2024;[Epub] CrossRef
Surgical treatment of movement disorders in neurometabolic conditions
Alonso Zea Vera, Andrea L. Gropman
Frontiers in Neurology.2023;[Epub] CrossRef

Case Report

Effect of Chelation Therapy on a Korean Patient With Brain Manganese Deposition Resulting From a Compound Heterozygous Mutation in the SLC39A14 Gene: Jae-Hyeok Lee, Jin-Hong Shin; J Mov Disord. 2022;15(2):171-174. Published online March 22, 2022; DOI: https://doi.org/10.14802/jmd.21143

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Abstract PDF

Mutations in the manganese transporter gene SLC39A14 lead to inherited disorders of manganese metabolism. Chelation therapy with edetate calcium disodium (CaNa2EDTA) is known to effectively reduce manganese deposition. We describe the first identified Korean case of SLC39A14-associated manganism and the treatment response to a 5-year chelation therapy. An 18-year-old female presented with childhood-onset dystonia. Magnetic resonance imaging showed T1 hyperintensity throughout the basal ganglia, brainstem, cerebellum, cerebral and cerebellar white matter, and pituitary gland. Blood manganese levels were elevated, and whole-exome sequencing revealed compound heterozygous mutations in SLC39A14. Treatment with intravenous CaNa₂EDTA led to a significant reduction in serum manganese levels and T1 hyperintensities. However, her dystonia improved insignificantly. Hence, early diagnosis of this genetic disorder is essential because it is potentially treatable. Even though our treatment did not significantly reverse the establish deficits, chelation therapy could have been more effective if it was started at an earlier stage of the disease.

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Brief communication

Utility of Clinical Exome Sequencing in Dystonia: A Single-Center Study From India: Vikram Venkappayya Holla, Koti Neeraja, Albert Stezin, Shweta Prasad, Bharat Kumar Surisetti, Manjunath Netravathi, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal; J Mov Disord. 2022;15(2):156-161. Published online March 16, 2022; DOI: https://doi.org/10.14802/jmd.21146

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Abstract PDF Supplementary Material

Objective
With the use of next-generation sequencing in clinical practice, several genetic etiologies of dystonia have been identified. This study aimed to ascertain the utility of clinical exome sequencing (CES) in dystonia and factors suggestive of a genetic etiology.
Methods
This study was a retrospective chart review of patients with dystonia who had undergone CES for the evaluation of dystonia.
Results
Forty-eight patients (35 males, 46 families) with dystonia were studied, with a mean age at onset of 16.0 ± 14.1 (1–58) years. A pathogenic/likely pathogenic variant was found in 20 patients (41.7%) among which 14 patients (29.2%) carried a novel variant. CES was more likely to detect a genetic diagnosis in patients with an early age at onset, i.e., ≤ 20 years.
Conclusion
CES is a useful tool in the diagnostic evaluation of dystonia, with a yield of close to 40%. Patients with an earlier age at onset have a higher likelihood of having dystonia due to a genetic cause than those with a later age at onset.

Citations

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Dissecting genetic architecture of rare dystonia: genetic, molecular and clinical insights
Burcu Atasu, Javier Simón-Sánchez, Hasmet Hanagasi, Basar Bilgic, Ann-Kathrin Hauser, Gamze Guven, Peter Heutink, Thomas Gasser, Ebba Lohmann
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Whole exome sequencing and clinical investigation of young onset dystonia: What can we learn?
Jong Hyeon Ahn, Ah Reum Kim, Woong-Yang Park, Jin Whan Cho, Jongkyu Park, Jinyoung Youn
Parkinsonism & Related Disorders.2023; 115: 105814. CrossRef

Review Article

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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472 Download
17 Web of Science
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Abstract PDF

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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Original Article

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.

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European Journal of Neurology.2025;[Epub] CrossRef
Case‐Fatality Rate in Parkinson's Disease: A Nationwide Registry Study
Jussi O.T. Sipilä, Valtteri Kaasinen, Päivi Rautava, Ville Kytö
Movement Disorders Clinical Practice.2024; 11(2): 152. CrossRef
Genome-wide determinants of mortality and motor progression in Parkinson’s disease
Manuela M. X. Tan, Michael A. Lawton, Miriam I. Pollard, Emmeline Brown, Raquel Real, Alejandro Martinez Carrasco, Samir Bekadar, Edwin Jabbari, Regina H. Reynolds, Hirotaka Iwaki, Cornelis Blauwendraat, Sofia Kanavou, Leon Hubbard, Naveed Malek, Katherin
npj Parkinson's Disease.2024;[Epub] CrossRef
Empowering the management of early-onset Parkinson’s disease: The role of technology
Roongroj Bhidayasiri, Ornanong Udomsirithamrong, Adrian de Leon, Walter Maetzler, Andrea Pilotto
Parkinsonism & Related Disorders.2024; 129: 107052. CrossRef
Different neurotoxicity and seeding activity between α-synuclein oligomers formed in plasma of patients with Parkinson’s disease and multiple system atrophy
Hanjiang Luo, Xiaohan Yu, Pengjie Li, Junya Hu, Wei Li, Xin Li, Min Chen, Shun Yu
Neuroscience.2024; 557: 1. CrossRef
Tinetti balance performance is associated with mortality in older adults with late-onset Parkinson’s disease: a longitudinal study
Louise Laurent, Pierre Koskas, Janina Estrada, Mélanie Sebbagh, Sophie Lacaille, Agathe Raynaud-Simon, Matthieu Lilamand
BMC Geriatrics.2023;[Epub] CrossRef
Letter in response to Cole-Hunter et al., 2023: What does “Parkinson’s disease mortality” mean?
Isabell Katharina Rumrich, Valtteri Kaasinen, Otto Hänninen, Sirpa Hartikainen, Anna-Maija Tolppanen
Environment International.2023; 173: 107852. CrossRef
Differences in Survival across Monogenic Forms of Parkinson's Disease
Aymeric Lanore, Fanny Casse, Christelle Tesson, Thomas Courtin, Poornima Jayadev Menon, Sara Sambin, Graziella Mangone, Louise‐Laure Mariani, Suzanne Lesage, Alexis Brice, Alexis Elbaz, Jean‐Christophe Corvol
Annals of Neurology.2023; 94(1): 123. CrossRef
Real-World Prescription Patterns For Patients With Young-Onset Parkinson’s Disease in China: A Trend Analysis From 2014 to 2019
Xiao-qin Liu, Xiao-yu Wang, Hui-ming Shen, Wen-yuan Pang, Ming-kang Zhong, Chun-lai Ma
Frontiers in Pharmacology.2022;[Epub] CrossRef
Montreal cognitive assessment (MoCA) is highly correlated with 1-year mortality in hip fracture patients
R. M. Y. Wong, R. W. K. Ng, W. W. Chau, W. H. Liu, S. K. H. Chow, C. Y. Tso, N. Tang, W.-H. Cheung
Osteoporosis International.2022; 33(10): 2185. CrossRef
Obituary for Jan O. Aasly (1950–2022)
Matthew J. Farrer
Movement Disorders.2022; 37(9): 1783. CrossRef
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
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Movement Disorders Clinical Practice.2022; 9(7): 869. CrossRef

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