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.
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.
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.
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.
Funded: Institute of Information & Communications Technology Planning & Evaluation, Ministry of Science and ICT, Korea Health Industry Development Institute, Ministry of Health and Welfare, Ministry of Education, National Research Foundation of Korea, Ewha Womans University
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.
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
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.
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Shed Syndecans (1–3), ELA-32, BDNF, NLR, and hs-CRP in Parkinson’s Disease: Appropriate Diagnostic and Prognostic Biomarkers When Combined in a Unique Panel Carmela Rita Balistreri, Daniele Magro, Letizia Scola, Paolo Aridon, Paolo Ragonese, Felipe Augusto Dos Santos Mendes, Giuseppe Schirò, Marco D’Amelio International Journal of Molecular Sciences.2025; 26(10): 4503. CrossRef
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.
Objective Gaits constitute the most fundamental and common form of human locomotion and are essential in daily activities. We aimed to investigate gait parameters in medically and cognitively healthy older adults to determine the independent effects of age, physical attributes, and cognition on these parameters.
Methods This retrospective study enrolled healthy older adult participants aged 50 years or older with normal cognition and no neurological symptoms or medical/surgical history that could affect gait. Quantitative gait analysis was conducted via the GAITRite Electronic Walkway, which categorizes gait parameters into spatiotemporal, spatial, temporal, phase, and variability. Gait parameters were compared between sexes across different age groups. The independent effects of age, Mini-Mental State Examination score, and physical characteristics were analyzed via a multiple regression model.
Results This study included 184 participants with an average age of 72.2 years. After adjusting for age, height, and footwear, only the base width and its variability differed between the sexes. Gait parameters varied significantly among different age groups, revealing multiple interparameter associations. Age was independently correlated with decreased velocity, step and stride lengths, single support time percentage and increased double support time, double support time percentage, and variability parameters, excluding the coefficient of variance of base width. Height was positively correlated with velocity, step and stride lengths, and base width, whereas leg length was negatively associated with cadence and positively associated with temporal parameters of gait.
Conclusion Gait parameters in healthy older adults were not only associated with age and physical characteristics but also had interparameter correlations.
Funded: Medical and Health Science and Technology Plan of Zhejiang Provincial Health Commission, Key Research and Development project of Zhejiang Province
Objective Huntington’s disease (HD) is characterized by motor, cognitive, and neuropsychiatric symptoms. Oculomotor impairments and gait variability have been independently considered as potential markers in HD. However, an integrated analysis of eye movement and gait is lacking. We performed multiple examinations of eye movement and gait variability in HTT mutation carriers, analyzed the consistency between these parameters and clinical severity, and then examined the associations between oculomotor impairments and gait deficits.
Methods We included 7 patients with pre-HD, 30 patients with HD and 30 age-matched controls. We collected demographic data and assessed the Unified Huntington’s Disease Rating Scale (UHDRS) score. Examinations, including saccades, smooth pursuit tests, and optokinetic (OPK) tests, were performed to evaluate eye movement function. The parameters of gait include stride length, walking velocity, step deviation, step length, and gait phase.
Results HD patients have significant impairments in the latency and velocity of saccades, the gain of smooth pursuit, and the gain and slow phase velocities of OPK tests. Only the speed of saccades significantly differed between pre-HD patients and controls. There are significant impairments in stride length, walking velocity, step length, and gait phase in HD patients. The parameters of eye movement and gait variability in HD patients were consistent with the UHDRS scores. There were significant correlations between eye movement and gait parameters.
Conclusion Our results show that eye movement and gait are impaired in HD patients and that the speed of saccades is impaired early in pre-HD. Eye movement and gait abnormalities in HD patients are significantly correlated with clinical disease severity.
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Transcranial magnetic stimulation-based neuroplasticity in the treatment of amblyopia Yilong Lin, Kaifang Cai Journal of Neuroscience Methods.2025; 419: 110464. CrossRef
Objective Oculomotor impairment is an important diagnostic feature of progressive supranuclear palsy (PSP) and PSP subtypes. We assessed the role of video-oculography (VOG) in confirming clinically suspected slow saccades in PSP and differentiating PSP from Parkinson’s disease (PD). We also measured the correlation of both saccadic velocity and latency in PSP patients with scores on the PSP Rating Scale, Montreal Cognitive Assessment, and frontal assessment battery. We assessed the frequency of apraxia of eyelid opening (ALO) and reflex blepharospasm in PSP and PD patients.
Methods A total of 112 PSP patients with slow saccades but not gaze palsy, 50 PD patients, and 50 healthy controls (HCs) were recruited. The Movement Disorders Society task force-PSP and PD criteria were used for the diagnoses. All the subjects underwent VOG.
Results Horizontal and vertical saccadic velocities and latencies differentiated PSP patients from PD patients and HCs (p<0.001). Vertical saccadic velocity and latency accurately differentiated PSP with predominant parkinsonism (PSP-P) patients from PD patients (p<0.001 and 0.012, respectively). A couple of vertical and horizontal saccadic velocities differentiated PSP-Richardson’s syndrome (PSP-RS) patients from PSP-P patients (vertical velocity of left eye: p=0.024; horizontal velocity of right eye: p=0.030). In vertical gaze, the mean velocity cutoff showed good sensitivity and specificity in differentiating PSP patients from HCs and PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse global cognitive and frontal dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.
Conclusion VOG is useful for confirming slow saccades in PSP-RS and PSP-P patients and for differentiating PSP-P patients from PD patients. Prolonged horizontal gaze latency was associated with more severe PSP and worse cognitive dysfunction. ALO and reflex blepharospasm were observed only in PSP patients.
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.
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.