Reorganization of motor network in patients with Parkinson's disease after deep brain stimulation.

AIMS: Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement-related brain regions in PD patients during the microlesion phase through seed-based FC analysis. METHODS: The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed-based FC analysis. Meanwhile, their relationship with the motor scale was investigated. RESULTS: The motor-related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS. CONCLUSION: The movement-related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post-DBS.

The severity assessment of Parkinson's disease based on plasma inflammatory factors and third ventricle width by transcranial sonography.

BACKGROUND: Predicting Parkinson's disease (PD) can provide patients with targeted therapies. However, disease severity can be roughly evaluated in clinical practice based on the patient's symptoms and signs. OBJECTIVE: The current study attempted to explore the factors linked with PD severity and construct a predictive model. METHOD: The PD patients and healthy controls were recruited from our study center while recording their basic demographic information. The serum inflammatory markers levels, such as Cystatin C (Cys C), C-reactive protein (CRP), RANTES (regulated on activation, normal T cell expressed and secreted), Interleukin-10 (IL-10), and Interleukin-6 (IL-6) were determined for all the participants. PD patients were categorized into early and mid-advanced groups based on the Hoehn and Yahr (H-Y) scale and evaluated using PD-related scales. LASSO logistic regression analysis (Model C) helped select variables based on clinical scale evaluations, serum inflammatory factor levels, and transcranial sonography measurements. The optimal harmonious model coefficient λ was determined via 10-fold cross-validation. Moreover, Model C was compared with multivariate (Model A) and stepwise (Model B) logistic regression. The area under the curve (AUC) of a receiver operator characteristic (ROC), brier score, calibration curve, and decision curve analysis (DCA) helped determine the discrimination and calibration of the predictive model, followed by configuring a forest plot and column chart. RESULTS: The study included 113 healthy individuals and 102 PD patients, with 26 early and 76 mid-advanced patients. Univariate analysis of variance screened out statistically significant differences among inflammatory markers Cys C and RANTES. The average Cys C level in the mid-advanced stage was significantly higher than in the early stage (p < 0.001) but not for RANTES (p = 0.740). The LASSO logistic regression model (λ.1se = 0.061) associated with UPDRS-I, UPDRS-II, UPDRS-III, HAMA, PDQ-39, and Cys C as the included independent variables revealed that the Model C discrimination and calibration (AUC = 0.968, Brier = 0.049) were superior to Model A (AUC = 0.926, Brier = 0.079) and Model B (AUC = 0.929, Brier = 0.071) models. CONCLUSION: The study results show multiple factors are linked with PD assessment. Moreover, the inflammatory marker Cys C and transcranial sonography measurement could objectively predict PD symptom severity, helping doctors monitor PD evolution in patients while targeting interventions.

The guiding effect of local field potential during deep brain stimulation surgery for programming in Parkinson's disease patients.

BACKGROUND: Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery require subsequent programming, which is complex and cumbersome. The local field potential (LFP) in the deep brain is associated with motor symptom improvement. The current study aimed to identify LFP biomarkers correlated with improved motor symptoms in PD patients after DBS and verify their guiding role in postoperative programming. METHODS: Initially, the study included 36 PD patients undergoing DBS surgery. Temporary external electrical stimulation was performed during electrode implantation, and LFP signals around the electrode contacts were collected before and after stimulation. The stimulating contact at 6 months of programming was regarded as the optimal and effective stimulating contact. The LFP signal of this contact during surgery was analyzed to identify potential LFP biomarkers. Next, we randomly assigned another 30 PD patients who had undergone DBS to physician empirical programming and LFP biomarker-guided programming groups and compared the outcomes. RESULTS: In the first part of the study, LFP signals of electrode contacts changed after electrical stimulation. Electrical stimulation reduced gamma energy and the beta/alpha oscillation ratio. The different programming method groups were compared, indicating the superiority of beta/alpha oscillations ratio-guided programming over physician experience programming for patients' improvement rate (IR) of UPDRS-III. There were no significant differences in the IR of UPDRS-III, post-LED, IR-PDQ39, number of programmings, and the contact change rate between the gamma oscillations-guided programming and empirical programming groups. CONCLUSION: Overall, the findings reveal that gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming in PD patients after DBS. Instead of relying solely on spike action potential signals from single neurons, LFP biomarkers can provide the appropriate depth for electrode placement.

Bilateral globus pallidus interna deep brain stimulation in the treatment of mixed cerebral palsy in ataxia with dyskinesia: a case report.

Background: Cerebral palsy (CP), a complex syndrome with multiple etiologies, is characterized by a range of movement disorders within the hypokinetic and hyperkinetic spectrum (dystonia or choreoathetosis). CP is often accompanied by neurological and psychiatric signs, such as spasticity, ataxia, and cognitive disorders. Although current treatment options for CP include pharmacological interventions, rehabilitation programs, and spasticity relief surgery, their effectiveness remains limited. Deep brain stimulation (DBS) has demonstrated significant effectiveness in managing dyskinesia; however, its potential therapeutic effect on CP remains determined. Methods: We present a case of a 44-year-old Asian female who was born as a twin with neonatal ischemic-hypoxic encephalopathy due to prolonged labor and delivery. She was diagnosed with CP at the age of 1 year. The patient exhibited delayed development compared to her peers and presented with various symptoms, including slurred speech, broad-based gait, horseshoe inversion of the right lower extremity, involuntary shaking of the upper extremities bilaterally, and hypotonia and showed no improvement with levodopa therapy. Two years ago, she developed progressive head tremors, which worsened during periods of tension and improved during sleep. As medical treatments proved ineffective and there were no contraindications to surgery, we performed bilateral globus pallidus interna DBS (GPi-DBS) to alleviate her motor dysfunction. Results: Following a 6-month follow-up, the patient demonstrated significant improvements in motor symptoms, including head and limb tremors and dystonia. In addition, significant improvement was observed in her overall psychological well-being, as evidenced by reduced anxiety and depression levels. Conclusion: DBS is an effective treatment for dyskinesia symptoms associated with CP in adults. Moreover, its effectiveness may continue to increase over time.

Effect of deep brain stimulation compared with drug therapy alone on the progression of Parkinson's disease.

Background: Parkinson's disease (PD) symptoms deteriorate with disease progression. Although deep brain stimulation (DBS) can effectively improve the motor signs of PD patients, it is not yet known whether DBS surgery, which is an invasive treatment modality, may change the progression of PD. Objective: The aim of this work was to compare the effect of DBS with that of drug treatment on the progression of PD. Methods: A total of 77 patients with PD with the Hoehn and Yahr scale (HY) stage of 2.5 or 3 were included, and were divided into 34 in the drug therapy alone group (Drug-G) and 43 in the DBS therapy group (DBS-G). All patients were subjected to a follow-up of 2 years, and disease severity was assessed by the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), the Montreal Cognitive Assessment (MOCA), the Hamilton Anxiety Scale (HAMA), and the Hamilton Depression Scale (HAMD) scores. In addition, the quality of life of patients and the burden on their family were assessed by the 39-item PD questionnaire (PDQ-39) scores, daily levodopa equivalent dose (LED), patient's annual treatment-related costs, and the Zarit Caregiver Burden Scale (ZCBS) score. The changes in relevant scale scores between the two groups were compared at each follow-up stage. Results: The UPDRS-III score of the patients in the "off" state increased from year to year in both groups, and the degree of increase of this score was greater in the DBS-G than in the Drug-G group. The MOCA score in both groups began to decline in the 2nd year of follow-up, and the decline was greater in the Drug-G than in the DBS-G group. DBS treatment did not affect patients' psychiatric disorders. The PDQ39, LED, costs, and ZCBS were negatively correlated with the follow-up time in patients in the DBS-G group, and positively correlated with the follow-up time in patients in the Drug-G. Conclusion: PD is progressive regardless of treatment. The findings from this follow-up study suggest that the disease progression of patients in DBS-G may be slightly faster compared to the drug-G, but the advantages of DBS are also evident. Indeed, DBS better improves patient's motor signs and quality of life and reduces the family burden. In addition, DBS has less impact on patients in terms of cognitive and mental effects.

Immunogenicity and protective efficacy induced by an mRNA vaccine encoding gD antigen against pseudorabies virus infection.

Messenger RNA-based vaccines represent new tools with prophylactic and therapeutic potential characterized by high flexibility of application for infectious diseases. Pseudorabies virus (PRV) is one of the major viruses affecting the pig industry. PRV has serious effects in piglets, sows, and growing-fattening pigs and can lead to huge economic losses. In this study, an envelope glycoprotein D (gD) gene-based specific mRNA vaccine was generated, and a mouse model was used to investigate the protective efficacy of the vaccine. The gD mRNA vaccine and the recombinant plasmid pVAX-gD were transfected into BHK21 cells, and the antigenicity of the expressed proteins was detected by Western blot analysis. Groups of mice were vaccinated with the gD mRNA vaccine, pVAX-gD, and PBS. T cell immune responses were measured by flow cytometry or ELISA and serum neutralization tests every two weeks. The challenge with the PRV-XJ strain was performed eight weeks after the primary immunization, and the response was monitored for 15 days. The levels of specific and neutralizing antibodies in the gD mRNA vaccine group were significantly increased in 8 weeks compared to those in the control group, and cytokine levels, including that of IFN-γ/IL-2, were considerably higher than those in the control animal. Additionally, the proportion of CD4+/CD8+ cells in peripheral lymphocytes was remarkably increased. Our data demonstrate that mRNA is a promising and effective tool for the development of vaccines. The PRV-gD-based mRNA vaccine can elicit an efficient neutralizing antibody response and induce effective protection in mice in defense against PRV infection.