Focused Ultrasound Thalamotomy for Tremor Relief in Atypical Parkisnsonism
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Parkinson’s Disease publishes research related to the epidemiology, etiology, pathogenesis, genetics, cellular, molecular and neurophysiology, as well as the diagnosis and treatment of Parkinson’s disease.
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Chief Editor Dr Cristine Alves da Costa is based at Centre National de la Research Scientifique, France. Her research is focuses on Parkinson’s molecular and cell biology.
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More articlesTransfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson’s Disease
In Parkinson’s disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson’s model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.
Improvement by Medication Less than Expected in Parkinson’s Disease: Blinded Evaluation of Levodopa Response
Background. The latest Movement Disorder Society (MDS) diagnostic criteria require a good and sustained response to medication to get a diagnosis of Parkinson’s disease, PD. Objective. The aim of this study was to evaluate levodopa response in a group of patients with probable PD, diagnosed by movement disorder specialists. Methods. An acute levodopa challenge test (LDCT) was performed after pausing the dopaminergic medication for 6 half-times. The motor part of the Unified Parkinson’s Disease Rating Scale was performed in the OFF-state and after LDCT (ON). A good effect was defined as >30% improvement. A video-protocol was used to secure standardized motor examination with blinded assessments of the UPDRS-III OFF and ON. An age-matched group of control subjects (CS) was included but did not go through LDCT. All participants were evaluated with Montreal Cognitive Assessment (MoCA) and Beck’s Depression Inventory (BDI). Results. In the statistical analysis, 37 patients were included. Twenty-one patients showed an improvement ≤30%, while 16 patients showed an improvement >30%. LDCT showed an overall mean improvement of 27.3% of motor UPDRS. In 43.2%, there was a discrepancy between the effect seen with the LDCT and the patients’ self-perceived medicine evaluation. Patients with PD had a significantly lower MoCA score and more depressive symptoms compared to CS. Conclusions. We showed an acute effect of levodopa using LDCT that was around 30% improvement. While it lends support to the use of this limit in the MDS diagnostic criteria, an acute effect of less than 30% should be considered acceptable in some patients. Our study highlights a discrepancy in the objective measure of medicine effect on motor symptoms and the patient’s subjective evaluation.
Preoperative Attention/Memory Problem Affects the Quality of Life of Parkinson’s Disease Patients after Deep Brain Stimulation: A Cohort Study
Objectives. The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Methods. Ninety-three patients diagnosed with Parkinson’s disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson’s Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson’s Disease Questionnaire (PDQ-8), respectively. Results. Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (β = 0.869, ) and the preoperative attention/memory subscore (β = −0.154, ) were predictive of the postsurgery improvement in quality of life (QoL). Conclusion. Deep brain stimulation (DBS) led to an improvement in the patients’ nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients’ quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.
A Systematic Review and Meta-Analysis of the Efficacy and Safety of Rasagiline or Pramipexole in the Treatment of Early Parkinson’s Disease
Background. Rasagiline or pramipexole monotherapy has been suggested for the management of early Parkinson’s disease (PD). The aim of this research was to systematically review the clinical efficacy and safety of rasagiline or pramipexole in early PD (defined as disease duration ≤5 years and Hoehn and Yahr stage of ≤3). Methods. Randomized controlled trials (RCTs) of rasagiline or pramipexole for early PD published up to September 2021 were retrieved. Outcomes of interest included changes in the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts II and III and the incidence of adverse events. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated, and heterogeneity was measured with the I2 test. Results. Nine rasagiline and eleven pramipexole RCTs were included. One post hoc analysis of one rasagiline study was included. Five studies for each drug were included in meta-analyses of the UPDRS scores. The rasagiline meta-analysis focused on patients receiving 1 mg/day. Rasagiline and pramipexole significantly improved UPDRS Part II and III scores when compared to placebo. Significant heterogeneity among the studies was present (I2 > 70%). Neither rasagiline nor pramipexole increased the relative risk for any adverse events, serious adverse events, or adverse events leading to withdrawal when compared with placebo. Conclusion. Applying a Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach to summarize the evidence, we found moderate confidence in the body of evidence for the efficacy of rasagiline or pramipexole in early PD, suggesting further well-designed, multicenter comparative RCTs remain needed.
Alprazolam Reduces Freezing of Gait (FOG) and Improves FOG-Related Gait Deficiencies
Background. Freezing of gait (FOG) is an intractable motor symptom in Parkinson’s disease (PD) that increases fall risk and impairs the quality of life. FOG has been associated with anxiety, with experimental support for the notion that anxiety itself provokes FOG. We investigated the effect of acute anxiety reduction via alprazolam on FOG in PD. Methods. In ten patients with PD, FOG, and normal cognition, we administered 0.25 mg alprazolam in one session and placebo in another, in counterbalanced order. At each session, on separate days, patients walked on a pressure-sensitive walkway. Using Oculus Rift virtual-reality goggles, patients walked along a plank that appeared to be (a) level with the floor, in the low-anxiety condition or (b) raised high above the ground, in the high-anxiety conditions. In this way, we assessed the impacts of anxiety and alprazolam (i.e., anxiety reduction) on FOG frequency and other gait parameters. Results. FOG events appeared only in the high-anxiety conditions. Alprazolam significantly reduced subjective and objective measures of anxiety, as well as the prevalence of FOG (). Furthermore, alprazolam improved swing time () and gait variability in all conditions, particularly during the elevated plank trials. Interpretation. Our results suggest that (1) anxiety induces FOG, and (2) alprazolam concomitantly reduces anxiety and FOG. Alprazolam further improved gait stability (i.e., swing time and gait variability). These findings reveal that anxiety triggers FOG in PD. Treating anxiety can reduce FOG and improve gait stability, potentially offering new therapeutic avenues for this intractable and disabling symptom in PD.
Single-Cell Analyses Reveal Necroptosis’s Potential Role in Neuron Degeneration and Show Enhanced Neuron-Immune Cell Interaction in Parkinson’s Disease Progression
Parkinson’s disease (PD) is a common neuron degenerative disease among the old, characterized by uncontrollable movements and an impaired posture. Although widely investigated on its pathology and treatment, the disease remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) has been applied to the area of PD, providing valuable data for related research. However, few works have taken deeper insights into the causes of neuron death and cell-cell interaction between the cell types in the brain. Our bioinformatics analyses revealed necroptosis-related genes (NRGs) enrichment in neuron degeneration and selecting the cells by NRGs levels showed two subtypes within the main degenerative cell types in the midbrain. NRG-low subtype was largely replaced by NRG-high subtype in the patients, indicating the striking change of cell state related to necroptosis in PD progression. Moreover, we carried out cell-cell interaction analyses between cell types and found that microglia (MG)’s interaction strength with glutamatergic neuron (GLU), GABAergic neuron (GABA), and dopaminergic neuron (DA) was significantly upregulated in PD. Also, MG show much stronger interaction with NRG-high subtypes and a stronger cell killing function in PD samples. Additionally, we identified CLDN11 as a novel interaction pattern specific to necroptosis neurons and MG. We also found LEF1 and TCF4 as key transcriptional regulators in neuron degeneration. These findings suggest that MG were significantly overactivated in PD patients to clear abnormal neurons, especially the NRG-high cells, explaining the neuron inflammation in PD. Our analyses provide insights into the causes of neuron death and inflammation in PD from single-cell resolution, which could be seriously considered in clinical trials.