Neurotransmitter changes in patients with Parkinson’s disease detected by encephalofluctuography technology: A non-randomized control study

BACKGROUND： Encephalofluctuograph Technology （ET） is an advanced and non-traumatic analytical method of brain function. ET can acquire super-slow waves from electroencephalic signals. Studies have shown that these particular spectra can reflect neurochemical processes in the brain. OBJECTIVE： To verify neurotransmitter changes in the brains Parkinson＇s disease （PD） patients through the use of ET. DESIGN, TIME AND SETTING： A non-randomized concurrent control experiment was performed at the Department of Neurology in Southern Building, General Hospital of Chinese PLA from August to December 2007. PARTICIPANTS： Sixty-one outpatients with PD were selected from the General Hospital of Chinese PLA from August 2007 to December 2007. In addition, 48 healthy subjects were selected as normal controls. METHODS： All patients underwent assessment of the sub scale Ⅱ, Ⅲ and V of the Unified Parkinson＇s Disease Rating Scale （UPDRS）, in which part Ⅱ was used to inform activity of daily living, part Ⅲ reflected athletic ability, and part Ⅴ was the Hoehn ＆ Yahr grade for symptoms evaluation. Correlation analysis was performed between dopamine levels and UPDRS assessment. Neurotransmitter changes were observed forty-eight prior to and 1.5 hours after medicating with Benserazide. The S1, S2, S4, S5, S7, and S 11 spectras respectively reflect gamma-aminobutyric acid （GABA）, glutamic acid （Glu）, 5-hydroxytryptamine （5-HT）, acetylcholine （ACh）, norepinephrine, and dopamine. MAIN OUTCOME MEASURES： Neurotransmitter changes in the brains of all subjects, and correlations between dopamine concentrations and UPDRS assessment. Neurotransmitter changes in a subgroup of patients prior to and 1.5 hours after medicating with Benserazide. RESULTS： Concentrations of 5-HT, ACh, and norepinephrine were decreased in the PD group, and GABA was increased. However, there was no significant difference compared with the normal control group （P 〉 0.05）. The level of dopamine in PD group was significantly lower than that in the control group （P 〈 0.01 ）. Dopamine concentrations in PD patients negatively correlated with UPDRS scores and the Hoehn ＆Yahr grade range （r = 0.4601, -0.4301, P 〈 0.01）. Dopamine levels increased significantly in PD patients 1.5 hours after medicating with Benserazide compared with before （P 〈 0.01）. CONCLUSION： Detection by ET demonstrated that dopamine concentrations were significantly decreased in the brains of PD patients, as well as played a role in the course of pathogenesis and therapy. These results provided useful information for future non-traumatic of PD.

Depression in Patients with Parkinson’s Disease and the Associated Features

The study was aimed to examine the prevalence of depression in patients with Parkinson’s disease （PD） and identify its features. A total of 131 out-patients, diagnosed as having idiopathic PD in accordance with the United Kingdom Parkinson’s Disease Society Brain Bank criteria, were interviewed with questionnaire and evaluated by Mini-Mental State Examination （MMSE）, Unified Parkinson’s Disease Rating Scale （UPDRS）, Hohen ＆Yahr staging （H＆Y staging） and Hamilton Rating Scale for Depression （HRSD）. Patients were divided into three groups in terms of HRSD score： depression group, sub-threshold depression group and non-depression group. The clinical variables and symptom profiles were obtained and compared among the three groups. The results showed that 27 patients （20.6%） fell into the depression group, 71 （54.2%） into the sub-threshold depression group, and 33 （25.2%） into the non-depression group. There were no differences in age, gender or tremor score among the groups （P〉0.05）. Significant differences were found in duration of PD, UPDRS score, rigidity score and H＆Y stage between the sub-threshold depression group （or the depression group） and the non-depression group （P〈0.05）. Moreover, the clinical variables in the subthreshold depression group had the trend of increasing with the severity of PD and their values were similar to those in the depression group. Anhedonia, feeling of incapability, sleep disturbance, gastrointestinal symptoms and depressive moods were most common in the depression group. And these symptoms also were more common in the other two groups. It is concluded that depression and sub-threshold depression are common in PD and share similar clinical features. Furthermore, subthreshold depression might be the prodrome of depression and may develop into depression as the condition progresses.

The Relationship among Caregiver Burden, Demographic Variables, and the Clinical Characteristics of Patients with Parkinson’s Disease—A Systematic Review of Studies Using Various Caregiver Burden Instruments

Caring for a person with Parkinson’s disease (PD) extends far beyond the ordinary exchange of assistance among people in a close relationship. Caregivers must learn to cope with the patient’s increasing disability and loss of independence. The aim of this systematic review was to critically assess and summarize the evidence of the influence of the demographic and clinical characteristics of patients with PD on caregiver burden by means of a caregiver burden instrument. In order to identify articles, electronic databases and reference lists were searched using the search word “Parkinson’s disease” in combination with “caregiver” or “carer” and with “burden” or “distress” or “stress” or “strain”. Thirty one articles were deemed eligible for inclusion. The methodological quality of the studies was evaluated. No studies were excluded due to low quality. The results revealed similar associations among caregiver burden, demographic variables and patient characteristics, across different caregiver burden instruments and various clinical scales. Higher PD stage and functional disability are the non-motor characteristics that contribute the most to caregiver burden. However, when comparing the impact of patient motor and non-motor symptoms, several studies found that mental symptoms had a stronger impact on caregiver burden than motor symptoms. No association was observed between caregiver burden and patient and caregiver demographics with the exception of the sub-scale analysis of caregiver burden in various age groups. Interpreting the results of studies that employ a range of different clinical assessment scales and burden instruments makes it challenging to provide a valid summary of caregiver burden in PD. The most commonly used analysis methods contribute little information about burden variation across caregiver groups or which areas are the most burdensome for caregivers. There is a need for a more uniform use of recommended instruments and for longitudinal studies.

Research on the effects of family care degree on stigma and psychosocial adaptation among the patients with Parkinson’s disease

Objective:This study aimed to investigate the status quo of family care degree,stigma and psychosocial adaptation of the patients with Parkinson’s disease(PD),and discuss the effects of family care degree on stigma and psychosocial adaptation among the patients with PD.Methods:This study was conducted between September 2018 and April 2019 on patients with PD who were admitted to a Ter tiary Grade A hospital in Dalian city.A total of 246 PD patients were investigated by convenience sampling method using self-designed general information questionnaire,along with family care index(APGAR),24-item Stigma Scale for Chronic Illness(SSCI),and Psychosocial Adjustment Scale(PAS)for PD.And patients were divided into two groups according to the level of family care degree and compared with stigma and psychosocial adaptation.Results:The total score of family care for patients with PD was 6.97±2.46,family function was good in 132 cases(53.7%),moderate barrier in 92 cases(37.4%),and severe barrier in 22 cases(8.9%).The scores of stigma and psychosocial adaptability and their dimensions in the group with high degree family care were higher than the low degree group.Conclusions:The overall level of family care for PD patients was poor.Improving family care degree can help patients with PD to reduce stigma and improve psychosocial adaptation.

Five-Year Outcomes of Bilateral Subthalamic Nucleus Stimulation in Japanese Patients with Parkinson’s Disease

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS. However, the long-term outcomes in Japanese patients have not been reported. Methods: We studied the long-term outcomes of STN DBS in Japanese patients with PD. Fifty-five consecutive patients treated with bilateral STN DBS were followed for 5 years after surgery. Each patient underwent Unified Parkinson’s Disease Rating Scale assessments preoperatively and 1 and 5 years after surgery. Results: Twelve patients (22%) were lost to follow up within 5 years. Among them, 7 died and 5 became bed ridden because of PD deterioration. In the 43 patients followed for 5 years, STN DBS significantly improved motor function. The cardinal motor symptoms of tremor, rigidity, and bradykinesia in medication-on periods were significantly better than baseline 5 years after DBS. However, axial motor symptoms of speech, gait and postural stability gradually deteriorated and significantly worsened 5 years after DBS. Motor complications, including dyskinesia and motor fluctuations, significantly improved after DBS with a marked reduction in dopaminergic medication. These effects were maintained 5 years after DBS. Frequently, persisting adverse effects included apraxia of eyelid opening and dysarthria. Conclusions: STN DBS significantly improved motor symptoms in patients with advanced PD. These effects were maintained over 5 years in most patients. However, some showed rapid PD progression even after STN DBS. Other treatments for the axial symptoms and disease progression are needed in long-term PD treatment.

Effect of Abnormal Posture on Quality of Life in Patients with Parkinson’s Disease

Background: Relationship between abnormal posture and QOL of Parkinson's disease is not clear. Objectives: To clarify the association between quality of life (QOL) and abnormal posture in patients with Parkinson’s disease (PD) and examine which QOL dimensions are involved. Methods: This study retrospectively examined PD patients (n = 57) who had undergone outpatient rehabilitation between January and March 2014. Evaluation items were Modified Hoehn Yahr (H-Y) stage, Unified Parkinson’s Disease Rating Scale (UPDRS)-Part III score, Timed Up and Go test (TUG, 3-m walking) result, Parkinson’s Disease Questionnaire (PDQ)-39 score, and the angle of forward and lateral trunk flexion in the standing position. Statistical analysis was performed to reveal the relationship between the total PDQ-39 score and individual evaluation items and which QOL dimensions were affected by abnormal posture due to forward or lateral flexion. Results: A total of 38 PD patients (17 men, 21 women;mean age, 73.2 ± 8.6 years) were enrolled. Among the evaluation items, lateral flexion angle showed a significant correlation with the total PDQ-39 score (r = 0.422, P = 0.008). PDQ-39 dimensions showing an association with forward flexion were activities of daily living (ADL) (P = 0.002) and communication (P = 0.007), whereas ADL (P = 0.004), communication (P = 0.021), and social support (P = 0.029) were associated with lateral flexion. Mobility was not associated with forward or lateral flexion. Conclusion: The present findings revealed a correlation between lateral flexion and QOL in PD patients. Among the PDQ-39 dimensions, ADL and communication were associated with abnormal posture.

Frequency of Comorbid Musculoskeletal Problems in Patients with Parkinson’s Disease: What and When?

Background: Musculoskeletal problems, deteriorating posture and pain are common complaints/comorbidities in Parkinson’s disease (PD). The aim of this study was to investigate the frequency of comorbid musculoskeletal problems in PD, and their relationship with disease stage and severity. Methods: The study was approved by the local ethical committee of Duzce University numbered with 2018/52 on date 26.03.2018. Patients with PD (pwPD) underwent a detailed examination to investigate the possible comorbidity of musculoskeletal findings in the orthopedics and traumatology clinic. Socio-demographic features, disease characteristics, motor and non-motor scores were recorded. Results: Thirty-seven pwPD were enrolled in the study. Mean age was 68.75 ± 10.75 years. Comorbid musculoskeletal problems were rotator cuff syndrome (27%), knee osteoarthritis (24.3%), meniscus (13.5%), lumber disc herniation (10.8%), kyphosis (8.1%), myotendinous diseases (16.3%). Rotator-cuff disease and knee osteoarthritis were most common comorbidities, especially in the “mild” and “moderate” stages of pwPD. Conclusion: Since most of the pwPD, especially the ones that have musculoskeletal complaints prior to the diagnosis of PD, present to the orthopedics and traumatology clinics or physiotherapists, it is mandatory to enhance the awareness of the orthopedic surgeons, and physiotherapy specialist in order to keep PD in mind.

Effects of Physical Activity Levels on Fatigue Perception in Patients with Parkinson’s Disease and Neurologically Healthy Individuals

Background: Recent researches involving fatigue and Parkinson’s disease (PD) sought to verify its incidence and the impacts of fatigue on quality life of patients with PD. Despite the importance of regular physical activity practice, there are only few studies that verified the influence of the levels of physical activity on fatigue in patients with PD. Objective: The aim of this study was to compare perception of fatigue between individuals with PD and neurologically healthy individuals (control group), considering the physical activity levels;and to verify the relation between physical activity levels and fatigue dimensions for individuals with PD and control group. Methods: Eighty individuals (40 patients with PD and 40 control individuals) participated in this study. Physical activity levels were evaluated through Modified Baecke Questionnaire for Older Adults. Multidimensional Fatigue Inventory (MFI) was used in order to evaluate fatigue dimensions (general, physical and mental fatigue, reduced motivation and activity). MANOVA two-way and Pearson linear correlation test were performed to analyze the data. Results: Patients with PD presented higher levels of fatigue, in all dimensions evaluated by MFI, comparing to control individuals. There was no association between physical activity levels and perception of fatigue for patients with PD and control individuals. Conclusion: Patients with PD showed increased perception of fatigue when compared to control individuals, due to PD characteristics. In addition, the perception of fatigue’s symptom was not influenced and had no relation by the level of physical activity.

Clinical Experience with Generic Rasagiline (Ralago^®) in Patients with Parkinson’s Disease: An Open-Label, Multicenter, Observational Study

Background: Antiparkinsonian pharmacotherapy represents one of the most important expenses related to Parkinson’s disease. The application of generic drugs may help to reduce the economic burden of the disease;however, efficacy and safety of these products have been less studied. Objective: To investigate the efficacy and safety of generic rasagiline (Ralago?) from a clinical perspective. Methods: The Clinical Global Impression of Severity scale was used to rate the most important motor and non-motor symptoms at baseline and 12 weeks after the initiation of Ralago?. Patients also identified symptoms which were the main sources of their disability and distress in everyday life. Results: A total of 499 patients were enrolled (231 females, mean age: 73.2 ± 9.1 years, mean duration of disease: 3.6 ± 3.7 years). Of them, 486 patients completed the study protocol. Both motor and non-motor symptoms showed improvement during 12-week Ralago? treatment. Adverse events were rare, and the majority of them were not considered as serious. Conclusions: The generic rasagiline (Ralago?) is an effective and safe generic product.

Safety and Efficacy of a Transdermal Rotigotine for the Treatment of Fatigue and Quality of Life in Patients with Parkinson’s Disease

Aim: To evaluate safety and efficacy of a transdermal rotigotine for the treatment of fatigue and quality of life (QOL) in patients with Parkinson’s disease (PD). This was a multi-sites open-label study of 58 PD patients (male 26, female 32) who met a Japanese PD diagnosis criterion. They received a transdermal rotigotine 4.5 mg/day for 8 weeks. We added a rotigotine on the previous anti-Parkinson’s drugs. Clinical signs were evaluated by Hoehn-Yahr (H-Y) stage, unified Parkinson’s disease rating scale (UPDRS), fatigue severity scale (FSS), and Euro quality of life (QOL). The scores of UPDRS improved from 35.2 ± 8.0 (mean ± SD) to 31.8 ± 8.3 (P = 0.14). There was no significant improvement or worsening of the H-Y stages. The scores of FSS improved from 57.3 ± 12.7 (mean ± SD) to 50.1 ± 11.8 (P = 0.061). The scores of QOL improved from 38.1 ± 11.1 to 48.3 ± 10.0 (P = 0.068). Our data demonstrate that, in a small sample size, administration of a transdermal rotigotine was associated with few side effects and was modestly effective for the treatment of fatigue and QOL in patients with PD.

Low Frequency of Leisure-Time Activities Correlates with Cognitive Decline and Apathy in Patients with Parkinson’s Disease

Objective: The purpose of this study is to investigate habitual leisure-time activities (physical and non-physical leisure activities) in patients with Parkinson’s disease (PD), and to determine any potential benefits of these activities on cognitive functions and emotional symptoms. Methods: Thirty-two patients with PD and 25 demographically-matched healthy controls participated in the present study. Neuropsychological tests (Wisconsin Card Sorting Test, Trail Making Test, Digit Span Test, Verbal Fluency Test, and Japanese Verbal Learning Test), assessment of emotional sym- ptoms, and interviews for confirmation of habitual leisure-time activities were conducted for all participants. Results: Patients with PD significantly showed the lower frequency of both physical and non-physical leisure activities than healthy controls. Compared to patients who engaged in physical leisure activities, patients who did not engage in such activities performed worse on the Trail Making Test (TMT-B, and TMT-B minus A). Moreover, patients who engaged in non-physical leisure activities were less apathetic than patients who did not engage in such activities. Conclusions: Our preliminary study shows that habitual leisure-time activities correlate with cognitive function and emotions in patients with PD. Reducing sedentary lifestyles and promoting habitual leisure-time activities may be helpful for preventing cognitive decline and apathy.

Serum Protein Level Is Related to ADL in Patients with Parkinson’s Disease

Objectives: To establish an ADL prediction model for Parkinson’s inpatients as an auxiliary evaluation scheme. Methods: The data of Parkinson’s patients hospitalized in the Department of Neurology of Affiliated Brain Hospital of Guangzhou Medical University from 2019 to 2022, which suited the criteria were collected, and a multiple linear regression model was established with serum total protein, serum albumin, age, BMI and education level as independent variables and BI scores as dependent variables. Results: A total of 95 PD patients were included (mean 70.05 ± 10.87 years): 53 males and 42 females. The correlation analysis showed that the serum total protein (r = 0.398, P Conclusion: The ADL multiple linear regression model can be used as an important means to evaluate the ADL ability of PD patients in hospital.

Treatment of Bilateral Proximal Humeral Fracture in Patients with Parkinson’s Disease: A Case Report

There are only a few reports about upper extremity fractures in patients with Parkinson’s disease (PD). This is a case report of a PD patient with severe tremors who had proximal humeral fracture. We performed surgery for the left side and conservative treatment for the right side. The patient was a 73-year-old woman who had been diagnosed with PD 10 years prior to presentation. Open reduction internal fixation was conducted for the left proximal humeral fracture. 7 months after the left shoulder fracture, she fell resulting in a right proximal humeral fracture for which she underwent conservative treatment. Although bone union was obtained bilaterally, anterior subluxation occurred in the operated side 9 months postoperative. Screw remove was performed because perforation of the screw was observed in the humeral head and was causing pain. Currently, restriction in range of motion and subluxation may be seen on the side that received conservative treatment, although pain is absent and patient satisfaction is high. On the operated side, there is a marked restriction in range of motion, subluxation, and pain. Our experience revealed that conservative treatment was effective for proximal humeral fractures and that optimal bone union might be obtained even in patients with suboptimal PD control.

Lack of Association between Impulse Control Disorders and REM Sleep Behavior Disorder in Patients with Parkinson’s Disease

Purpose: Rapid eye movement sleep behavior disorder (RBD) and impulse control disorders (ICDs) are common in subjects with Parkinson’s disease. The association between these two conditions has been contradictory. The aim of this study is to analyze the association between these two non-motor symptoms. Methods: Consecutive subjects with Parkinson’s disease attending the Movement Disorders Outpatient Clinic were included. The presence of ICDs was assessed using the Questionnaire for Impulse Control Disorders Rating Scale. RBD was diagnosed by an overnight, single night polysomnography. Results: Fifty-five consecutive subjects with Parkinson’s disease were included. The prevalence of ICDs and related behaviors was 23.6% (ICD in 14.5% and related behaviors in 9.1%). RBD was diagnosed in 47.2% of the patients. No differences were found in the frequency of ICDs and related behaviors when comparing subjects with and without RBD (23% versus 24.1%, p = 0.926, respectively). Conclusion: No association between the presence of RBD and the frequency of ICDs in subjects with Parkinson’s disease was found.

Quantitative EEG Changes in Patients with Parkinson’s Disease during Therapy with Rasagiline

It has been suggested that in patients with Parkinson’s disease (PD) metabolism of the MAO-B inhibitor selegiline to methamphetamine may contribute and/or exacerbate sleep problems, possibly leading to deficits of cognition. This open-label exploratory study included 30 PD patients currently being treated with selegiline (7.5 mg/day) and complaining of sleep disturbances. The aim of the study was to determine whether switching from selegiline to another MAO-B inhibitor without amphetamine-like metabolites, namely rasagiline, would improve sleep behaviour and cognitive function in PD patients. Pathologic aberrations as determined by comparison of the frequency pattern of patients to a database consisting of healthy subjects revealed an approximation of electric brain activity to normality. For verification of efficacy, a combination of questionnaires, quantitative source density EEG recording with CATEEMò and performance of two psychometric tasks (d2-test of attention and reading) during the EEG recording were done on the last day of selegiline treatment (7.5 mg/day) as well as 2 and 4 months later, during which the patients were treated with rasagiline (1 mg/day). In addition, performance of the mental tasks revealed a statistically significant (p < 0.05) increase of theta power (4.75 - 6.75 Hz) indicative of improved cognitive abilities at the end of the treatment period. At the same time evaluation of the psychometric test results indicated a statistical improvement with respect to the score of the d2-test (increase from 6.54 to 7.37;p < 0.05). Serum levels of methamphetamine were measured before and after intake of selegiline or rasagiline. They were correlated to alpha2 power, which is under dopaminergic control, within the temporal lobe. From these results it is concluded that the switch from selegiline to rasagiline not only improved sleep behaviour as reported separately but also had a positive effect on electric brain activity and on cognition in these patients.

The Impact and Intervention of Handheld Tai Chi Water-Resistance Fitness Ball on Middle-Aged and Elderly Patients with Parkinson’s Disease

Through the use of a survey and statistical methods, this study explores the effects and interventions of handheld Tai Chi water resistance fitness balls on the elderly with Parkinson’s disease. Firstly, a questionnaire on exercise compliance for patients with Parkinson’s disease was developed, and its reliability and validity were tested. Then, a survey was conducted to investigate the current status of exercise compliance among Parkinson’s disease patients, including general information, scoring status, and single and multiple factor analyses of influencing factors [1]. The results of the study show that through qualitative research, the dimensions and item pools of the questionnaire were initially constructed, and the reliability analysis of the questionnaire was conducted through Delphi expert consultation, with favorable results in terms of its reliability and validity [2]. Regarding the current status of exercise compliance among Parkinson’s disease patients, the study found that the level of exercise compliance needs improvement, and there are significant differences in exercise compliance levels among patients under different circumstances. Finally, the research results were discussed and conclusions were drawn. The innovation of this study lies in the development of a questionnaire on exercise compliance for patients with Parkinson’s disease and the preliminary qualitative research and Delphi expert consultation conducted on it, providing new ideas and methods for the study of exercise compliance. However, the study also has limitations as it did not examine the effects of other interventions on Parkinson’s disease, so further research should be conducted [3].

Design of a Biomedical Device to Reduce Anxiety Experienced by Patients Diagnosed with Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disease that occurs due to loss of nerve cells that produce dopamine in the brain, affecting approximately 4 million people worldwide. PD patients often feel an increase in anxiety levels daily. While there are medications/exercises to help relieve anxiety, there are limited methods to reduce anxiety without the help of a caretaker. As a result, MEDIC Foundation, a non-profit organization in British Columbia, Canada, is designing an automated system that consists of a wristband and an application which uses vi-bration therapy to help reduce anxiety of PD patients. Literature reviews were conducted to document the project’s needs. Phase I of the project focused on de-veloping a prototype for the application and phase II on developing the wrist-band. The team developed prototypes of a wristband that automatically applies vibration near the median nerve as the heart rate variability (HRV) deviates away from the normal threshold of the user, and an application that displays real-time heart rate variability signals as well as provides for relaxation. The development of the prototype is still in early progress. By creating this automated system, we aim to provide a solution to senior PD patients to relieve anxiety independently. .

Expectations and Level of Satisfaction of the Patient with Parkinson’s Disease Undergoing Deep Brain Stimulation Surgery at the National Institute of Neurology and Neurosurgery

Background: Deep brain stimulation (DBS) is an established treatment for patients with advanced Parkinson’s disease (PD). Reports show continued patient satisfaction after surgery despite not maintaining clinical improvement as measured by evolution scales. Objectives: The present study sought to explore expectations and level of satisfaction in patients after DBS surgery with a semi-structured questionnaire and subsequent correlation with functional scales, Quality of Life (QoL), and motor and non-motor symptoms. Methods: We performed descriptive statistics to represent demographic data, Wilcoxon rank tests to determine significant differences, and Spearman correlation between the applied scales. Results: We evaluated 20 patients with a history of DBS surgery. 45% were female, with a mean age of 55.7 ± 14.15 years, a mean disease duration of 13.42 ± 8.3 years, and a mean time after surgery of 3.18 ± 1.86 years. Patients reported surgery meeting expectations in 85.5% and continued satisfaction in 92%. These two variables showed a significant correlation. Conclusions: This sample of patients remained satisfied after DBS surgery, although we found no differences in motor and non-motor clinimetric scales. Further studies are needed to confirm the importance of assessing quality of life in patients with DBS.

Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.

Effects of mesenchymal stem cell on dopaminergic neurons,motor and memory functions in animal models of Parkinson's disease:a systematic review and meta-analysis

Parkinson’s disease is chara cterized by the loss of dopaminergic neurons in the substantia nigra pars com pacta,and although restoring striatal dopamine levels may improve symptoms,no treatment can cure or reve rse the disease itself.Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson’s disease.Mesenchymal stem cells are considered a promising option due to fewer ethical concerns,a lower risk of immune rejection,and a lower risk of teratogenicity.We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function,memory,and preservation of dopamine rgic neurons in a Parkinson’s disease animal model.We searched bibliographic databases(PubMed/MEDLINE,Embase,CENTRAL,Scopus,and Web of Science)to identify articles and included only pee r-reviewed in vivo interve ntional animal studies published in any language through J une 28,2023.The study utilized the random-effect model to estimate the 95%confidence intervals(CI)of the standard mean differences(SMD)between the treatment and control groups.We use the systematic review center for laboratory animal expe rimentation’s risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment.A total of 33studies with data from 840 Parkinson’s disease model animals were included in the meta-analysis.Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test.Among the stem cell types,the bone marrow MSCs with neurotrophic factor group showed la rgest effect size(SMD[95%CI]=-6.21[-9.50 to-2.93],P=0.0001,I^(2)=0.0%).The stem cell treatment group had significantly more tyrosine hydroxylase positive dopamine rgic neurons in the striatum([95%CI]=1.04[0.59 to 1.49],P=0.0001,I^(2)=65.1%)and substantia nigra(SMD[95%CI]=1.38[0.89 to 1.87],P=0.0001,I^(2)=75.3%),indicating a protective effect on dopaminergic neurons.Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route(SMD[95%CI]=-2.59[-3.25 to-1.94],P=0.0001,I^(2)=74.4%).The memory test showed significant improvement only in the intravenous route(SMD[95%CI]=4.80[1.84 to 7.76],P=0.027,I^(2)=79.6%).Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson’s disease.Further research is required to determine the optimal stem cell types,modifications,transplanted cell numbe rs,and delivery methods for these protocols.