Journal of Movement Disorders最新文献

Objective: To evaluate the efficacy of istradefylline in Parkinson's disease patients experiencing motor fluctuations with and without dyskinesia and characterize potential predictors for treatment-emergent dyskinesia with istradefylline.

Methods: Pooled analysis of 8 phase 2b/3 trials of istradefylline (20 or 40 mg/day) versus placebo.

Results: Data from 2,719 patients, 56% of whom presented with baseline dyskinesia, were analyzed post hoc. The presence of baseline dyskinesia did not affect the mean decrease in "OFF" time with dyskinesia, increase in "ON" time without troublesome dyskinesia, or improvement in the Unified Parkinson's Disease Rating Scale motor score associated with istradefylline treatment. Dyskinesia was reported in 17% of patients receiving istradefylline, with higher rates for women (21%), patients with a BMI <18.5 kg/m2 (22%), and patients receiving catechol-o-methyltransferase inhibitors plus dopamine agonists (22%) and monoamine oxidase B inhibitors (25%).

Conclusion: Istradefylline treatment resulted in greater reductions in total "OFF" hours/day and increases in "ON" time without troublesome dyskinesia than did placebo, regardless of the presence or absence of preexisting dyskinesia.

Objective: Delayed ON is a condition in which Parkinson's disease (PD) patients do not experience the effect of levodopa in time after taking the dosage. The ability of various oral levodopa regimens to overcome this problem has been poorly investigated. To evaluate the efficacy of levodopa/benserazide dispersible tablets in PD patients with delayed ON to the first morning dose.

Methods: This multicenter, randomized, crossover trial involved 40 eligible PD patients with delayed ON. The participants were randomized to receive either levodopa/benserazide 100 mg dispersible or regular tablets for 4 weeks, followed by a one-week wash-out interval and an alternate drug for another 4 weeks. Participants took the investigational drug with the first morning dose of their antiparkinsonian medications. Other medications were not changed during the trial. The primary outcome was changes in time-to-ON after the first-morning dose recorded in a special diary before and after each therapy. We also evaluated changes in parkinsonism, motor fluctuations, and dyskinesia using the Unified PD Rating Scale and the Unified Dyskinesia Rating Scale. Finally, we investigated whether efficacy was affected by Helicobacter pylori status via baseline serum samples from every participant.

Results: Nine patients dropped out during the trial. The time-to-ON was significantly reduced by the dispersible tablet compared with the regular tablet (-34.72 vs. -23.81 minutes, p=0.014). There were no significant changes in parkinsonian severity or dyskinesia with either drug. The dispersible formulation was beneficial for both Helicobacter pylori-positive and -negative groups.

Conclusion: Levodopa/benserazide dispersible formulations can improve time-to-ON without exacerbating dyskinesia in PD patients suffering from delayed ON.

Research on the pathophysiology of Parkinson's disease (PD) has traditionally been performed with functional magnetic resonance imaging (fMRI); however, only a few studies have been conducted in longitudinal cohorts. In the present literature review, we aim to summarize the most recent progress in functional fMRI studies in prospective cohorts and, more specifically, in combination with other biomarkers to track the disease progression of PD. This review focuses on the potential application of multimodal longitudinal functional approaches based on the current evidence for the purpose of understanding disease progression and monitoring future therapeutic interventions.

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: 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.