The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency i...The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, th展开更多
Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but impr...Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.展开更多
Introduction: The Parkinson’s KinetiGraph (PKG) is a digital measurement system for motor fluctuations (FS). The aim of this study is to investigate whether FS, measured by the PKG, are associated with disease durati...Introduction: The Parkinson’s KinetiGraph (PKG) is a digital measurement system for motor fluctuations (FS). The aim of this study is to investigate whether FS, measured by the PKG, are associated with disease duration of Parkinson’s Disease (PD) patients. Material and Methods: 172 PD were included. PKG measurements, clinical data and disease duration were collected. Patients were categorized in four disease duration categories (0 - 5 years, 6 - 7 years, 8 - 11 years and ≥12 years). Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis. Results: The mean age of the patients is 69.2 years (SD ± 8.13). Disease duration varies between 1 and 28 years. Significant difference was found between the four disease categories in FS (p = 0.050);between group 1 - 3, p = 0.005. Conclusions: As expected, FS measured by PKG increase during disease progression in PD. In advanced disease stages, FS stabilise, indicating that PKG is the most useful in early and moderate stages of PD.展开更多
Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining th...Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is consid- ered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson＇s disease （four men and two women, aged 37-65 years）, who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson＇s Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 ps and frequency at 130 Hz. Voltage adjust- ment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov （identifier： NCT01934881）.展开更多
Background:There is an urgent need for developing objective,effective and convenient measurements to help clinicians accurately identify bradykinesia.The purpose of this study is to evaluate the accuracy of an objecti...Background:There is an urgent need for developing objective,effective and convenient measurements to help clinicians accurately identify bradykinesia.The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping(FT)that uses evolutionary algorithms(EAs)and explore whether it can be used to identify early stage Parkinson’s disease(PD).Methods:One hundred and seven PD,41 essential tremor(ET)patients and 49 normal controls(NC)were recruited.Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger.Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs.The output from the device(referred to as"PD-Monitor")scaled from−1 to+1(where higher scores indicate greater severity of bradykinesia).Meanwhile,the bradykinesia was rated clinically using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale(MDS-UPDRS)FT item.Results:With an increasing MDS-UPDRS FT score,the PD-Monitor score from the same hand side increased correspondingly.PD-Monitor score correlated well with MDS-UPDRS FT score(right side:r=0.819,P=0.000;left side:r=0.783,P=0.000).Moreover,PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup(FT bradykinesia scored from 1 to 3)were all higher than that in NC.Receiver operating characteristic(ROC)curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy(≥89.7%)in the right dominant hand.Furthermore,PD-Monitor scores could discriminate early stage PD from NC,with area under the ROC curve greater than or equal to 0.899.Additionally,ET without bradykinesia could be differentiated from PD by PD-Monitor scores.A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides.Conclusions:Our study demonstrated that a simple to use device employing classifiers derived from EAs展开更多
AIM： To evaluate the feasibility of a new clinical rating scale for a standardized assessment of cirrhosis-associated neuro-psychiatric symptoms. METHODS： Forty patients with liver cirrhosis （LC, with or without lo...AIM： To evaluate the feasibility of a new clinical rating scale for a standardized assessment of cirrhosis-associated neuro-psychiatric symptoms. METHODS： Forty patients with liver cirrhosis （LC, with or without low-grade hepatic encephalopathy） were investigated using a clinical neuro-psychiatric rating scale based on a comprehensive list of neurological, psychomotor, cognitive, affective, behavioral symptoms, and symptoms of disturbed bioregulation. RESULTS： The analysis revealed that the majodty of cirrhotic patients showed, besides characteristic neurological symptoms of hepatic encephalopathy, various psychomotor, affective and bioregulatory symptoms （disturbed sleep and sexual dysfunction）. Patients were impaired in the following subscales： sleep and biorhythm disorder （75.0% of patients）, Parkinsonoid symptoms （25.0%）, affective symptoms （17.5%）, and psychomotor retardation （12.5%）. The increase of total neuro-psychiatric clinical score was significantly associated with the degree of hepatic encephalopathy. CONCLUSION： This study suggests that a substantial number of patients with LC and low-grade hepatic encephalopathy manifest various clinical neuro-psychiatric symptoms. The use of a rating scale, which explores clinical dimensions of hepatic encephalopathy, would improve the management of patients with LC.展开更多
基金supported by the National Natural Science Foundation of China,No.31771143 (to QZ)Shanghai Municipal Science and Technology Major Project,ZJ Lab+1 种基金Shanghai Center for Brain Science and Brain-Inspired Technology,No.2018SHZDZX01 (to LC)Shanghai Zhou Liangfu Medical Development Foundation “Brain Science and Brain Diseases Youth Innovation Program”(to ZQ)。
文摘The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the composition of the globus pallidus neurons, th
基金We thank Ms Fahmida Zaman for her initial intellectual support for this projectWe are grateful to Ms Noshin Noorjahan for her editorial support for our manuscript.Department of Pharmaceutical Sciences at North South University provided the Laboratory space,including the equipment and basic reagents necessary to conduct this project.
文摘Background:Parkinson's disease(PD)is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide.The current therapies for PD are symptom-based;they do not provide a cure but improve the quality of life.Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis.Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS.Therefore,in this study,we investigated the role of Epalrestat in the reserpine induced mouse model of PD.Method:We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia,muscular rigidity,palpebral ptosis,and tremor,as well as conducting swim and open field tests.Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.Results:Epalrestat treatment significantly improved akinesia and bradykinesia,muscular dysfunctions,tremor level,and gait functions compared to the reserpine group.It also improved the latency in the swim test.Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes,glutathione,catalase,and superoxide dismutase.Furthermore,Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.Conclusion:Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.
文摘Introduction: The Parkinson’s KinetiGraph (PKG) is a digital measurement system for motor fluctuations (FS). The aim of this study is to investigate whether FS, measured by the PKG, are associated with disease duration of Parkinson’s Disease (PD) patients. Material and Methods: 172 PD were included. PKG measurements, clinical data and disease duration were collected. Patients were categorized in four disease duration categories (0 - 5 years, 6 - 7 years, 8 - 11 years and ≥12 years). Kruskal-Wallis and Mann-Whitney U tests were used for statistical analysis. Results: The mean age of the patients is 69.2 years (SD ± 8.13). Disease duration varies between 1 and 28 years. Significant difference was found between the four disease categories in FS (p = 0.050);between group 1 - 3, p = 0.005. Conclusions: As expected, FS measured by PKG increase during disease progression in PD. In advanced disease stages, FS stabilise, indicating that PKG is the most useful in early and moderate stages of PD.
基金supported by the Science and Technology Foundation of Guangdong Province of China,No.2014A030304019the Natural Science Foundation of Guangdong Province of China,No.2015A030313164
文摘Deep brain stimulation of the subthalamic nucleus is recognized as the most effective treatment for moderate and advanced Parkinson＇s disease. Programming of the stimulation parameters is important for maintaining the efficacy of deep brain stimulation. Voltage is consid- ered to be the most effective programming parameter. The present study is a retrospective analysis of six patients with Parkinson＇s disease （four men and two women, aged 37-65 years）, who underwent bilateral deep brain stimulation of the subthalamic nucleus at the First Affiliated Hospital of Sun Yat-sen University, China, and who subsequently adjusted only the stimulation voltage. We evaluated motor symptom severity using the Unified Parkinson＇s Disease Rating Scale Part III, symptom progression using the Hoehn and Yahr scale, and the levodopa equivalent daily dose, before surgery and 1 and 2 years after surgery. The 2-year follow-up results show that rigidity and tremor improved, and clinical symptoms were reduced, while pulse width was maintained at 60 ps and frequency at 130 Hz. Voltage adjust- ment alone is particularly suitable for patients who cannot tolerate multiparameter program adjustment. Levodopa equivalent daily dose was markedly reduced 1 and 2 years after surgery compared with baseline. Our results confirm that rigidity, tremor and bradykinesia can be best alleviated by voltage adjustment. The trial was registered at ClinicalTrials.gov （identifier： NCT01934881）.
基金This work was supported by the National Natural Science Foundation of China(grant numbers.81430022,81771374).
文摘Background:There is an urgent need for developing objective,effective and convenient measurements to help clinicians accurately identify bradykinesia.The purpose of this study is to evaluate the accuracy of an objective approach assessing bradykinesia in finger tapping(FT)that uses evolutionary algorithms(EAs)and explore whether it can be used to identify early stage Parkinson’s disease(PD).Methods:One hundred and seven PD,41 essential tremor(ET)patients and 49 normal controls(NC)were recruited.Participants performed a standard FT task with two electromagnetic tracking sensors attached to the thumb and index finger.Readings from the sensors were transmitted to a tablet computer and subsequently analyzed by using EAs.The output from the device(referred to as"PD-Monitor")scaled from−1 to+1(where higher scores indicate greater severity of bradykinesia).Meanwhile,the bradykinesia was rated clinically using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale(MDS-UPDRS)FT item.Results:With an increasing MDS-UPDRS FT score,the PD-Monitor score from the same hand side increased correspondingly.PD-Monitor score correlated well with MDS-UPDRS FT score(right side:r=0.819,P=0.000;left side:r=0.783,P=0.000).Moreover,PD-Monitor scores in 97 PD patients with MDS-UPDRS FT bradykinesia and each PD subgroup(FT bradykinesia scored from 1 to 3)were all higher than that in NC.Receiver operating characteristic(ROC)curves revealed that PD-Monitor FT scores could detect different severity of bradykinesia with high accuracy(≥89.7%)in the right dominant hand.Furthermore,PD-Monitor scores could discriminate early stage PD from NC,with area under the ROC curve greater than or equal to 0.899.Additionally,ET without bradykinesia could be differentiated from PD by PD-Monitor scores.A positive correlation of PD-Monitor scores with modified Hoehn and Yahr stage was found in the left hand sides.Conclusions:Our study demonstrated that a simple to use device employing classifiers derived from EAs
文摘AIM： To evaluate the feasibility of a new clinical rating scale for a standardized assessment of cirrhosis-associated neuro-psychiatric symptoms. METHODS： Forty patients with liver cirrhosis （LC, with or without low-grade hepatic encephalopathy） were investigated using a clinical neuro-psychiatric rating scale based on a comprehensive list of neurological, psychomotor, cognitive, affective, behavioral symptoms, and symptoms of disturbed bioregulation. RESULTS： The analysis revealed that the majodty of cirrhotic patients showed, besides characteristic neurological symptoms of hepatic encephalopathy, various psychomotor, affective and bioregulatory symptoms （disturbed sleep and sexual dysfunction）. Patients were impaired in the following subscales： sleep and biorhythm disorder （75.0% of patients）, Parkinsonoid symptoms （25.0%）, affective symptoms （17.5%）, and psychomotor retardation （12.5%）. The increase of total neuro-psychiatric clinical score was significantly associated with the degree of hepatic encephalopathy. CONCLUSION： This study suggests that a substantial number of patients with LC and low-grade hepatic encephalopathy manifest various clinical neuro-psychiatric symptoms. The use of a rating scale, which explores clinical dimensions of hepatic encephalopathy, would improve the management of patients with LC.
