Accepted articles
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Original Article
- Gait instability and compensatory mechanisms in Parkinson's disease with camptocormia: An exploratory study
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Hideyuki Urakami, Yasutaka Nikaido, Yuta Okuda, Yutaka Kikuchi, Ryuichi Saura, Yohei Okada
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Received November 8, 2024 Accepted December 27, 2024 Published online December 27, 2024
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DOI: https://doi.org/10.14802/jmd.24226
[Accepted]
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Abstract
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- 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.
Review Article
- Drug Repositioning and Repurposing for Disease-Modifying Effects in Parkinson’s Disease
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Seong Ho Jeong, Phil Hyu Lee
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Received January 15, 2025 Accepted February 7, 2025 Published online February 7, 2025
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DOI: https://doi.org/10.14802/jmd.25008
[Accepted]
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Abstract
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- 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
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Anil Dash, Farsana Mustafa, Divyani Garg, Sreeja Samineni, Ayush Agarwal, Ajay Garg, Achal Kumar Srivastava
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Received December 16, 2024 Accepted January 24, 2025 Published online January 31, 2025
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DOI: https://doi.org/10.14802/jmd.24259
[Accepted]
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- Diagnosing Cerebrotendinous Xanthomatosis in a Middle-Aged Woman with Cervical Dystonia
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Wei-Sheng Wang, Yu-Ping Chiu, Meng-Han Tsai, Shey-Lin Wu, Yen-Chung Chen
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Received September 28, 2024 Accepted January 17, 2025 Published online January 20, 2025
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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
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Tomonori Nukariya, Toshiki Tezuka, Shohei Okusa, Ryotaro Okochi, Yuto Sakai, Yoshihiro Nihei, Jin Nakahara, Morinobu Seki
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Received November 28, 2024 Accepted January 6, 2025 Published online January 6, 2025
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DOI: https://doi.org/10.14802/jmd.24247
[Accepted]
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- Two cases of genetically proven SCARB2-Related Progressive Myoclonic Epilepsy without renal failure: A report from India
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Pavankumar Katragadda, Vikram V Holla, Gautham Arunachal, Nitish Kamble, Ravi Yadav, Pramod Kumar Pal
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Received October 27, 2024 Accepted December 17, 2024 Published online December 27, 2024
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DOI: https://doi.org/10.14802/jmd.24222
[Accepted]
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Brief communications
- CSF1R-related adult-onset leukoencephalopathy with axonal spheroids: A case series of four Asian Indian patients
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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
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Received January 4, 2025 Accepted February 17, 2025 Published online February 17, 2025
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DOI: https://doi.org/10.14802/jmd.25004
[Accepted]
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Abstract
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- 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.
- Pre-DBS modified Tremor/Postural instability and gait difficulty score ratio as indicator of short-term outcome of subthalamic nucleus DBS in Parkinson’s disease
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Chakradhar Reddy, Kanchana Pillai, Shejoy Joshua, Anup Nair, Harshad Chavotiya, Manas Chacko, Asha Kishore
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Received August 5, 2024 Accepted January 2, 2025 Published online January 2, 2025
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DOI: https://doi.org/10.14802/jmd.24175
[Accepted]
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Abstract
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- Purpose
-The outcomes of motor and non-motor features of Parkinson’s disease (PD) following DBS vary among its subtypes. We tested whether pre-operative motor subtyping using the modified Tremor/PIGD ratio, could indicate the short-term motor, non-motor and quality of life (QOL) outcomes of STN-DBS.
Method
In this prospective study, 39 consecutive STN-DBS cases were assessed in Drug-OFF state before surgery and subtyped using the ratio of tremor and PIGD scores (T/P ratio). 6 months after surgery patients were reassessed in Stimulation ON-Drug OFF state and the percentage change in motor, non-motor and QOL scores (PDQ39) was calculated.
Results
The modified T/P ratio had a moderate, positive correlation with the percentage change in scores of UPDRS III in OFF, sum of cardinal motor signs, non-motor symptoms scale (NMSS) and quality of life (PDQ39).
Conclusion
Preoperative PD motor subtyping can be used as an indicator of the short-term, outcomes of STN-DBS in PD.
- Validation of the Korean Version of the Huntington’s Disease Quality of Life Battery for Carers
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Hee Jin Chang, Eungseok Oh, Won Tae Yoon, Chan Young Lee, Kyum-Yil Kwon, Yun Su Hwang, Chaewon Shin, Jee-Young Lee
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Received October 21, 2024 Accepted December 20, 2024 Published online December 30, 2024
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DOI: https://doi.org/10.14802/jmd.24217
[Accepted]
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Abstract
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- 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.
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