Journal of Movement Disorders

Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease: Seong Ho Jeong, Phil Hyu Lee; J Mov Disord. 2025;18(2):113-126. Published online February 7, 2025; DOI: https://doi.org/10.14802/jmd.25008

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Abstract PDF: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder and is characterized by progressive dopaminergic and nondopaminergic 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 patients with 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 promising approaches 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.

Gait Instability and Compensatory Mechanisms in Parkinson’s Disease Patients With Camptocormia: An Exploratory Study: Hideyuki Urakami, Yasutaka Nikaido, Yuta Okuda, Yutaka Kikuchi, Ryuichi Saura, Yohei Okada; J Mov Disord. 2025;18(2):127-137. Published online December 27, 2024; DOI: https://doi.org/10.14802/jmd.24226

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Abstract PDF Supplementary Material: Objective
Camptocormia contributes to vertical gait instability and, at times, may also lead to forward instability in experimental settings in Parkinson’s disease (PD) patients. 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 patients, 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 as well as 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. The significance level was set at 0.05.
Results
Excluding one unique case, the PD+CC group presented a significantly lower vertical center of mass (COM) position (p=0.019) increased mediolateral COM velocity (p=0.004) and step width (p=0.013), compared to the PD-CC group. Both PD groups presented greater anterior‒posterior margins of stability than did the 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).
Conclusion
Most PD+CC patients presented vertical gait instability, increased fall risk, and adopted compensatory strategies involving greater lateral COM shift and a 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 patients.

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; J Mov Disord. 2025;18(2):138-148. Published online February 27, 2025; DOI: https://doi.org/10.14802/jmd.24131

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Abstract PDF: Objective
We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence 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 whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth 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 (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score 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 of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the 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 nonlinear increasing (J-shaped) trend.
Conclusion
Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.

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; J Mov Disord. 2025;18(2):149-159. Published online March 14, 2025; DOI: https://doi.org/10.14802/jmd.24237

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

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; J Mov Disord. 2025;18(2):160-164. Published online December 30, 2024; DOI: https://doi.org/10.14802/jmd.24217

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Abstract PDF Supplementary Material: Objective
The Huntington’s Disease Quality of Life Battery for Carers (HDQoL-C) is used to evaluate caregiver quality of life. This study aimed to develop and validate the Korean version of the HDQoL-C (K-HDQoL-C) to assess the burden on Korean caregivers of Huntington’s disease (HD) patients.
Methods
A total of 19 HD caregivers (7 females, mean age 55.4±14.6 years) participated in this study. 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, 2 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
The internal consistencies of the K-HDQoL-C were 0.771 (part 2), 0.938 (part 3), and 0.891 (part 4). The test-retest reliability ranged from 0.908 to 0.936. Part 3 was negatively correlated with the ZBI-12, and part 4 was positively correlated with the ZBI-12 (r=-0.780, 0.923; p<0.001).
Conclusion
The K-HDQoL-C effectively evaluates the challenges faced by HD caregivers, particularly in terms of care aspects and life satisfaction.

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; J Mov Disord. 2025;18(2):165-169. Published online January 2, 2025; DOI: https://doi.org/10.14802/jmd.24175

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Abstract PDF Supplementary Material: 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.

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; J Mov Disord. 2025;18(2):170-174. Published online February 17, 2025; DOI: https://doi.org/10.14802/jmd.25004

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Abstract PDF: Objective
Colony-stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare adult-onset leukoencephalopathy. Reports of CSF1R-L patients from the Indian subcontinent remain limited. We aimed to report four patients with genetically confirmed CSF1R-L from four Asian Indian families and described their clinical, molecular, and radiological features.
Methods
All patients underwent clinical examination, brain magnetic resonance imaging, and whole-exome sequencing to identify causative variants in the CSF1R gene. We also reviewed published reports of Indian patients with CSF1R-L.
Results
The age at enrollment ranged from 34 to 40 years. The duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioral syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis was observed in one patient. We identified four different variants (three missense variants and one in-frame deletion). Radiological findings revealed white matter involvement and diffusion restriction involving the subcortical white matter and pyramidal tracts.
Conclusion
We expand the literature on CSF1R-L patients from India by reporting four new cases.

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; J Mov Disord. 2025;18(2):175-178. Published online December 27, 2024; DOI: https://doi.org/10.14802/jmd.24222

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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; J Mov Disord. 2025;18(2):179-181. Published online January 6, 2025; DOI: https://doi.org/10.14802/jmd.24247

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Cognitive and Psychiatric Adverse Effects of Foslevodopa/Foscarbidopa in Patients with Parkinson's Disease
Sacha Brohée, Emmanuel Roze, David Grabli, Hélène Letrillart, Lise Mantisi, Cendrine Foucard, Elodie Hainque, Florence Cormier, Aurélie Méneret, Fabien Hauw
Movement Disorders Clinical Practice.2025;[Epub] CrossRef

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; J Mov Disord. 2025;18(2):182-184. Published online January 20, 2025; DOI: https://doi.org/10.14802/jmd.24202

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Spastic Paraplegia 82 in Two Asian Indian Siblings With PCYT2 Mutations: Anil Dash, Farsana Mustafa, Divyani Garg, Sreeja Samineni, Ayush Agarwal, Ajay Garg, Achal Kumar Srivastava; J Mov Disord. 2025;18(2):185-189. Published online January 31, 2025; DOI: https://doi.org/10.14802/jmd.24259

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A Chinese Child With Dystonia Linked to the EIF2AK2 Missense Variant: A Case Report: Lifang Dai, Changhong Ren, Shenghan Guan, Xiaojuan Tian, Hui Xiong, Changhong Ding; J Mov Disord. 2025;18(2):190-192. Published online February 20, 2025; DOI: https://doi.org/10.14802/jmd.24215

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Early-Onset Cataracts as a Clinical Indicator of DJ-1-Related Parkinsonism: Sahil Mehta, Jagdeep Singh, Saurabh Mishra, Vivek Lal; J Mov Disord. 2025;18(2):193-195. Published online March 24, 2025; DOI: https://doi.org/10.14802/jmd.25016

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