Journal of Movement Disorders

Original Articles

Feasibility of a Multidomain Intervention for Safe Mobility in People with Parkinson’s Disease and Recurrent Falls: Natalie E Allen, Lina Goh, Colleen G Canning, Catherine Sherrington, Lindy Clemson, Jacqueline CT Close, Stephen R Lord, Simon J G Lewis, Simone Edwards, Susan Harkness, Roslyn Savage, Lyndell Webster, Genevieve Zelma, Serene S Paul; Received November 19, 2024 Accepted March 14, 2025 Published online March 14, 2025; DOI: https://doi.org/10.14802/jmd.24237 [Accepted]

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Abstract PDF: Objective
Mobility limitations and falls are common in people with Parkinson’s disease (PwP). A tailored, multidomain intervention has the potential to be more effective in improving mobility safety and preventing falls than exercise alone. This study aimed to explore the feasibility and potential effectiveness of a multidomain fall prevention intervention (Integrate) designed for PwP who fall frequently.
Methods
The home-based intervention was delivered over 6 months by occupational therapists and physiotherapists. The personalized intervention incorporated home fall-hazard reduction, exercise and safer mobility behavior training. Participants received 8 to 12 home visits, and where required, were supported by care-partners to undertake the intervention.
Results
Twenty-nine people (49% recruitment rate, 10% drop-out rate) with moderate to advanced Parkinson’s disease, a history of recurrent falls and mild to moderate cognitive impairment participated, with 26 completing the study. Adherence was moderate to high and there were no adverse events related to the intervention. Twenty-one (81%) participants met or exceeded their safer mobility goal on the Goal Attainment Scale. Participants had a median 1.0 point clinically meaningful improvement on the Short Physical Performance Battery. An exploratory analysis indicated fall rates reduced by almost 50% in the six-month follow-up period (IRR 0.51, 95% CI 0.28 – 0.92).
Conclusions
A multidomain occupational therapy and physiotherapy intervention for PwP with recurrent falls was feasible and appeared to improve mobility safety. A randomized trial powered to detect effects on falls and mobility is warranted.

The association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease: A nationwide cohort study: Yoonkyung Chang, Ju-young Park, Ji Young Yun, Tae-Jin Song; Received June 9, 2024 Accepted February 26, 2025 Published online February 27, 2025; DOI: https://doi.org/10.14802/jmd.24131 [Accepted]

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Abstract PDF: Objective
We aimed to investigate the association between the triglyceride-glucose index, which measures insulin resistance, and the incidence risk of Parkinson’s disease.
Methods
Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for which more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined using the code of the International Classification of Diseases 10th edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs.
Results
During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.48%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index scores was associated with a significantly increased risk of Parkinson’s disease (Hazard ratio (HR): 1.062, 95% confidence interval (CI): 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence risk of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093. 95% CI: 1.025–1.165), but not in a diabetes mellitus cohort (HR: 0.990, 95% CI: 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a non-linear increasing (J-shape) trend.
Conclusion
Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence risk of Parkinson’s disease in the general population, particularly in a non-diabetes mellitus cohort.

Letter to the editor

A Chinese child with dystonia linked to EIF2AK2 missense variant: a case report: Lifang Dai, Changhong Ren, Shenghan Guan, Xiaojuan Tian, Hui Xiong, Changhong Ding; Received October 20, 2024 Accepted February 19, 2025 Published online February 20, 2025; DOI: https://doi.org/10.14802/jmd.24215 [Accepted]

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Brief communication

CSF1R-related adult-onset leukoencephalopathy with axonal spheroids: A case series of four Asian Indian patients: Divyani Garg, Abhishek Vaingankar, Anu Gupta, Roopa Rajan, Ajay Garg, Ayush Agarwal, Farsana Mustafa, Divya M Radhakrishnan, Awadh Kishor Pandit, Venugopalan Y Vishnu, Mamta Bhushan Singh, Rohit Bhatia, Achal Kumar Srivastava; Received January 4, 2025 Accepted February 17, 2025 Published online February 17, 2025; DOI: https://doi.org/10.14802/jmd.25004 [Accepted]

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Abstract PDF: Background
Colony stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare, adult onset leukoencephalopathy. Descriptions from the Indian subcontinent remain limited.
Objective
To report four patients with genetically confirmed CSF1R-L from four Asian Indian families, describing clinical, molecular and radiological features.
Methods
All patients underwent clinical examination, MRI brain, and whole exome sequencing to identify causative variants in CSF1R gene. We also reviewed published Indian cases with CSF1R-L.
Results
Age at enrolment ranged from 34-40 years. Duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioural syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis in one patient. We identified four different variants (three missense, one inframe deletion). Radiological findings demonstrated white matter involvement, and diffusion restriction involving subcortical white matter and pyramidal tracts.
Conclusions
We expand the literature from India with four new cases of CSF1R-L.

Review Article

Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease: Seong Ho Jeong, Phil Hyu Lee; Received January 15, 2025 Accepted February 7, 2025 Published online February 7, 2025; DOI: https://doi.org/10.14802/jmd.25008 [Accepted]

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Abstract PDF: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and non-dopaminergic neuronal loss and the presence of Lewy bodies, which are primarily composed of aggregated α-synuclein. Despite advancements in symptomatic therapies, such as dopamine replacement and deep brain stimulation, no disease-modifying therapies (DMTs) have been identified to slow or arrest neurodegeneration in PD. Challenges in DMT development include disease heterogeneity, the absence of reliable biomarkers, and the multifaceted pathophysiology of PD, encompassing neuroinflammation, mitochondrial dysfunction, lysosomal impairment, and oxidative stress. Drug repositioning and repurposing strategies using existing drugs for new therapeutic applications offer a promising approach to accelerate the development of DMTs for PD. These strategies minimize time, cost, and risk by using compounds with established safety profiles. Prominent candidates include glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, ambroxol, calcium channel blockers, statins, iron-chelating agents, c-Abl inhibitors, and memantine. Although preclinical and early clinical studies have demonstrated encouraging results, numerous phase III trials have yielded unfavorable outcomes, elucidating the complexity of PD pathophysiology and the need for innovative trial designs. This review evaluates the potential of prioritized repurposed drugs for PD, focusing on their mechanisms, preclinical evidence, and clinical trial outcomes, and highlights the ongoing challenges and opportunities in this field.

Letters to the editor

Spastic paraplegia 82 in two Asian Indian siblings with PCYT2 mutation: Anil Dash, Farsana Mustafa, Divyani Garg, Sreeja Samineni, Ayush Agarwal, Ajay Garg, Achal Kumar Srivastava; Received December 16, 2024 Accepted January 24, 2025 Published online January 31, 2025; DOI: https://doi.org/10.14802/jmd.24259 [Accepted]

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Diagnosing Cerebrotendinous Xanthomatosis in a Middle-Aged Woman with Cervical Dystonia: Wei-Sheng Wang, Yu-Ping Chiu, Meng-Han Tsai, Shey-Lin Wu, Yen-Chung Chen; Received September 28, 2024 Accepted January 17, 2025 Published online January 20, 2025; DOI: https://doi.org/10.14802/jmd.24202 [Accepted]

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Levodopa Pharmacokinetics in Switching From Levodopa/Carbidopa Intestinal Gel to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion in a Patient With Parkinson’s Disease: A Case Report: Tomonori Nukariya, Toshiki Tezuka, Shohei Okusa, Ryotaro Okochi, Yuto Sakai, Yoshihiro Nihei, Jin Nakahara, Morinobu Seki; Received November 28, 2024 Accepted January 6, 2025 Published online January 6, 2025; DOI: https://doi.org/10.14802/jmd.24247 [Epub ahead of print]

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Brief communications

Modified Ratio of Tremor/Postural Instability Gait Difficulty Score as an Indicator of Short-Term Outcomes of Subthalamic Nucleus Deep Brain Stimulation in Parkinson’s Disease: Chakradhar Reddy, Kanchana Pillai, Shejoy Joshua, Anup Nair, Harshad Chavotiya, Manas Chacko, Asha Kishore; Received August 5, 2024 Accepted January 2, 2025 Published online January 2, 2025; DOI: https://doi.org/10.14802/jmd.24175 [Epub ahead of print]

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Abstract PDF: Objective
The outcomes of motor and nonmotor features of Parkinson’s disease (PD) following deep brain stimulation (DBS) vary among its subtypes. We tested whether preoperative motor subtyping using the modified tremor/postural instability and gait difficulty ratio (T/P ratio) could indicate the short-term motor, nonmotor and quality of life (QOL) outcomes of subthalamic nucleus (STN) DBS.
Methods
In this prospective study, 39 consecutive STN DBS patients were assessed in the drug-OFF state before surgery and subtyped according to the T/P ratio. Patients were reassessed 6 months after surgery in the stimulation ON-drug-OFF state, and the percentage changes in motor, nonmotor and QOL scores (Parkinson’s Disease Quality of Life Questionnaire [PDQ-39]) were calculated.
Results
The modified T/P ratio was moderately and positively correlated with the percentage change in the Unified Parkinson’s Disease Rating Scale III score in the OFF state, the sum of cardinal motor signs, the Non-Motor Symptom Scale score, and QOL (PDQ-39).
Conclusion
Preoperative PD motor subtyping can be used as an indicator of the short-term outcomes of STN DBS in PD patients.

Validation of the Korean Version of the Huntington’s Disease Quality of Life Battery for Carers: Hee Jin Chang, Eungseok Oh, Won Tae Yoon, Chan Young Lee, Kyum-Yil Kwon, Yun Su Hwang, Chaewon Shin, Jee-Young Lee; Received October 21, 2024 Accepted December 20, 2024 Published online December 30, 2024; DOI: https://doi.org/10.14802/jmd.24217 [Accepted]

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Abstract PDF: Objectives
The Huntington's Disease Quality of Life Battery for Carers (HDQoL-C) evaluates caregiver quality of life. This study aims to develop and validate the Korean version (K-HDQoL-C) to assess the burden on Korean caregivers of HD patients.
Methods
Nineteen HD caregivers (7 females, mean age 55.4±14.6 years) participated. The K-HDQoL-C, a translation of the English version, consisted of demographic information, caring aspects, life satisfaction, and feelings about life. It was administered twice, two weeks apart. Internal consistency was evaluated using Cronbach’s α, and test-retest reliability was assessed with intraclass correlation coefficients. The relationship with the Zarit Burden Interview-12 (ZBI-12) was analyzed.
Results
Internal consistencies of K-HDQoL-C were 0.771 (part 2), 0.938 (part 3), and 0.891 (part 4). Test-retest reliability ranged from 0.908 to 0.936. Part 3 negatively correlated with ZBI-12, and part 4 positively correlated (R = -0.780, 0.923; p < 0.001).
Conclusion
The K-HDQoL-C effectively evaluates challenges faced by HD caregivers, particularly in care aspects and life satisfaction.

Original Article

Gait instability and compensatory mechanisms in Parkinson's disease with camptocormia: An exploratory study: Hideyuki Urakami, Yasutaka Nikaido, Yuta Okuda, Yutaka Kikuchi, Ryuichi Saura, Yohei Okada; Received November 8, 2024 Accepted December 27, 2024 Published online December 27, 2024; DOI: https://doi.org/10.14802/jmd.24226 [Accepted]

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Abstract PDF: Objective
Camptocormia has been considered to contribute to vertical gait instability and, at times, may also lead to forward instability in experimental settings in Parkinson's disease (PD). However, these aspects, along with compensatory mechanisms, remain largely unexplored. This study comprehensively investigated gait instability and compensatory strategies in PD patients with camptocormia (PD+CC).
Methods
Ten PD+CC, 30 without camptocormia (PD-CC), and 27 healthy controls (HCs) participated. Self-paced gait tasks were analyzed using three-dimensional motion capture systems to assess gait stability, spatiotemporal, and kinematic parameters. Unique cases with pronounced forward gait stability or instability were first identified, followed by group comparisons. Correlation analysis was performed to examine associations between trunk flexion angles (lower/upper) and gait parameters. Significance level was set at 0.05.
Results
Excluding one unique case, the PD+CC group showed a significantly lower vertical center of mass (COM) position (p=0.019), along with increased mediolateral COM velocity (p=0.004) and step width (p=0.013), compared to PD-CC group. Both PD groups showed higher anterior-posterior margin of stability than HCs (p<0.001). Significant correlations were found between lower/upper trunk flexion angles and a lower vertical COM position (r=-0.690/-0.332), as well as increased mediolateral COM velocity (r=0.374/0.446) and step width (r=0.580/0.474).
Conclusions
Most PD+CC patients exhibited vertical gait instability, increasing fall risk, and adopted compensatory strategies involving greater lateral COM shift and wider base of support, with these trends intensifying as trunk flexion angles increased. These findings may guide targeted interventions for gait instability in PD+CC.

Letter to the editor

Two Cases of Genetically Proven SCARB2-Related Progressive Myoclonic Epilepsy Without Renal Failure: A Report From India: Pavankumar Katragadda, Vikram V Holla, Gautham Arunachal, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal; Received October 27, 2024 Accepted December 17, 2024 Published online December 27, 2024; DOI: https://doi.org/10.14802/jmd.24222 [Epub ahead of print]

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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; J Mov Disord. 2025;18(1):17-30. Published online December 26, 2024; DOI: https://doi.org/10.14802/jmd.24232

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Abstract PDF: This review provides a comprehensive framework for the diagnostic approach and management of Huntington’s disease (HD) tailored to the Korean population. Key topics include genetic counseling, predictive testing, and reproductive options like preimplantation genetic testing. Strategies for assessing disease progression in premanifest HD through laboratory investigations, biofluid, and imaging biomarkers are highlighted. Special considerations for juvenile and late-onset HD, along with associated comorbidities like diabetes mellitus, hypertension, and cardiovascular abnormalities, are discussed. The guide emphasizes personalized symptom management, including pharmacotherapy, physical therapy, and nutritional support, while exploring emerging disease-modifying treatments. A multidisciplinary care model is advocated to improve outcomes for HD patients and caregivers in Korea.

Brief communication

Spatiotemporal Gait Parameters During Turning and Imbalance in Parkinson’s Disease: Video-Based Analysis From a Single Camera: HoYoung Jeon, Jung Hwan Shin, Ri Yu, Min Kyung Kang, Seungmin Lee, Seoyeon Kim, Bora Jin, Kyung Ah Woo, Han-Joon Kim, Beomseok Jeon; J Mov Disord. 2025;18(1):87-92. Published online December 23, 2024; DOI: https://doi.org/10.14802/jmd.24210

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Abstract PDF Supplementary Material: Objective
This study aims to objectively evaluate turning gait parameters in Parkinson’s disease (PD) patients using 2D-RGB video-based analysis and explore their relationships with imbalance.
Methods
We prospectively enrolled PD patients for clinical assessment, balance analysis and gait with 180º turning. Spatiotemporal gait parameters during turning were derived using video-based analysis and correlated with modified Hoehn and Yahr (mHY) stages and center of pressure (COP) oscillations.
Results
A total of 64 PD patients were enrolled. The PD patients with higher mHY stages (≥2.5) had significantly longer turning times, greater numbers of steps, wider step bases and less variability in step length during turns. COP oscillations were positively correlated with the mean turning time on both the anterior-posterior and right-left axes.
Conclusion
Spatiotemporal gait parameter during turning, derived from video-based gait analysis, may represent apromising biomarker for monitoring postural instability in PD patients.

Review Article

Non-Motor Fluctuations in Parkinson’s Disease: Underdiagnosed Yet Important: Iro Boura, Karolina Poplawska-Domaszewicz, Cleanthe Spanaki, Rosabel Chen, Daniele Urso, Riaan van Coller, Alexander Storch, Kallol Ray Chaudhuri; J Mov Disord. 2025;18(1):1-16. Published online December 20, 2024; DOI: https://doi.org/10.14802/jmd.24227

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Abstract PDF: Non-motor fluctuations (NMFs) in Parkinson’s disease (PD) significantly affect patients’ well-being. Despite being identified over two decades ago, NMFs remain largely underrecognized, undertreated, and poorly understood. While they are often temporally associated with motor fluctuations (MFs) and can share common risk factors and pathophysiologic mechanisms, NMFs and MFs are currently considered distinct entities. The prevalence and severity of NMFs, often categorized into neuropsychiatric, sensory, and autonomic subtypes, vary significantly across studies due to the heterogeneous PD populations screened and the diverse evaluation tools applied. The consistent negative impact of NMFs on PD patients’ quality of life underscores the importance of further investigations via focused and controlled studies, validated assessment instruments and novel digital technologies. High-quality research is essential to illuminate the complex pathophysiology and clinical nuances of NMFs, ultimately enhancing clinicians’ diagnostic and treatment options in routine clinical practice.

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