Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to con...Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.展开更多
<strong>Background: </strong>Parkinson’s disease (PD) remains a challenge for neurologists, particularly in its advanced stages when non-motor symptoms become a burden for the patient. While motor symptom...<strong>Background: </strong>Parkinson’s disease (PD) remains a challenge for neurologists, particularly in its advanced stages when non-motor symptoms become a burden for the patient. While motor symptoms may be satisfactorily controlled with levodopa therapy or continuous levodopa/carbidopa intestinal gel (LCIG) administration, autonomic, sleep and mental disorders are hard to treat. During the last years, researchers have shifted their interest more to non-motor symptoms, PD being now considered a complex multiorgan impairment. <strong>Objective:</strong> The aim of this study was to describe non-motor symptoms in 40 Romanian patients diagnosed with PD, under conventional and LCIG administration treatment. <strong>Methods: </strong>A cross-sectional observational study was conducted, consisting of two groups of 20 patients each: the first group comprised PD patients who received conventional Levodopa treatment, while the second group was formed of patients receiving LCIG therapy. Various data concerning patient’s age, gender, duration of illness, comorbidities, motor and non-motor symptoms were recorded. The data were processed in SPSS v.20. <strong>Results: </strong>Subjects under continuous LCIG administration, although showing amelioration of motor symptoms, complained more frequently of constipation, mental, and sleeping disorders (statistically significant). Regarding anosmia, orthostatic hypotension, hypersalivation, urinary incontinence and restless legs syndrome, no statistical significant difference was observed between the two groups (p > 0.05). <strong>Conclusion:</strong> Nowadays, more research is conducted on non-motor symptoms in PD patients, as therapeutic measures try to limit these burdens, in order to improve patient’s quality of life.展开更多
Parkinson＇s disease （PD） is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neur...Parkinson＇s disease （PD） is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have dif- ferent rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.展开更多
Parkinson’s disease(PD)is the second most common and fastest-growing neurodegenerative disorder.In recent years,it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal...Parkinson’s disease(PD)is the second most common and fastest-growing neurodegenerative disorder.In recent years,it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis.However,little is known about whether and how the caudal zona incerta(ZIc)regulates parkinsonian motor symptoms.Here,we showed that specific glutamatergic but not GABAergic ZIc^(VgluT2) neurons regulated these symptoms.ZIc^(VgluT2) neuronal activation induced time-locked parkinsonian motor symptoms.In mouse models of PD,the ZIc^(VgluT2) neurons were hyperactive and inhibition of their activity ameliorated the motor deficits.ZIc^(VgluT2) neurons monosynaptically projected to the substantia nigra pars reticulata.Incerta-nigral circuit activation induced parkinsonian motor symptoms.Together,our findings provide a direct link between the ZIc,its glutamatergic neurons,and parkinsonian motor symptoms for the first time,help to better understand the mechanisms of PD,and supply a new important potential therapeutic target for PD.展开更多
Background Although the validity of non-motor symptoms screening questionnaire （NMSQuest） for Parkinson＇s disease has been verified in several recent researches, the specificity of the questionnaire is still in dou...Background Although the validity of non-motor symptoms screening questionnaire （NMSQuest） for Parkinson＇s disease has been verified in several recent researches, the specificity of the questionnaire is still in doubt. This study aimed to compare the non-motor symptoms （NMS） in Parkinson＇s disease （PD） with a medically ill control group. Methods In this study, the first comprehensive clinic-based NMS screening questionnaire for PD developed by the Parkinson＇s Disease Non-Motor Group （PDNMG） was used. Data from 90 PD patients and 270 sex-and age-matched control subjects, including stroke （n=90）, heart disease （n=-90） and diabetes （n=-90） were analyzed. Results Compared with control group, NMS was more common in PD; on an average, most PD patients reported more than 12 non-motor items. There was a correlation of total NMS score in PD patients with Hoehn ＆ Yahr Staging, but not with age, sex distribution, disease duration, or age at disease onset. Additionally, depression, constipation and impaired olfaction which occurred prior to the motor symptoms of PD were reported in this study. Conclusions NMS are more common in PD patients. There are some NMS that occurred at the preclinical stage of PD and might predict the onset of motor symptoms of PD patients.展开更多
Background:Tai Chi has been shown to improve motor symptoms in Parkinson’s disease(PD),but its long-term effects and the related mechanisms remain to be elucidated.In this study,we investigated the effects of long-te...Background:Tai Chi has been shown to improve motor symptoms in Parkinson’s disease(PD),but its long-term effects and the related mechanisms remain to be elucidated.In this study,we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms.Methods:Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi(n=32),brisk walk-ing(n=31)and no-exercise(n=32)groups.At baseline,6 months and 12 months during one-year intervention,all participants underwent motor symptom evaluation by Berg balance scale(BBS),Unified PD rating-scale(UPDRS),Timed Up and Go test(TUG)and 3D gait analysis,functional magnetic resonance imaging(fMRI),plasma cytokine and metabolomics analysis,and blood Huntingtin interaction protein 2(HIP2)mRNA level analysis.Longitudinal self-changes were calculated using repeated measures ANOVA.GEE(generalized estimating equations)was used to assess factors associated with the longitudinal data of rating scales.Switch rates were used for fMRI analysis.False discovery rate correction was used for multiple correction.Results:Participants in the Tai Chi group had better performance in BBS,UPDRS,TUG and step width.Besides,Tai Chi was advantageous over brisk walking in improving BBS and step width.The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β.The improvements in UPDRS were asso-ciated with enhanced default mode network function,decreased L-malic acid and 3-phosphoglyceric acid,and increased adenosine and HIP2 mRNA levels.In addition,arginine biosynthesis,urea cycle,tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training.Conclusions:Long-term Tai Chi training improves motor function,especially gait and balance,in PD.The underlying mechanisms may include enhanced brain network function,reduced inflammation,improved amino acid metabolism,energy metabolism and neurotransmitter metabolism,and decreased vulnerability to dopaminergic degeneration.Trial registration This study has been registered at Chinese Clinical Trial Registry(Registration number:ChiCTR2000036036;Registration date:August 22,2020).展开更多
Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analy...Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro- nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.展开更多
Motor symptoms are cardinal clinical features of Parkinson’s disease (PD). Progress in drug therapy and rehabilitation has been presenting beneficial effect for motor symptoms. However, non-motor symptoms and signs i...Motor symptoms are cardinal clinical features of Parkinson’s disease (PD). Progress in drug therapy and rehabilitation has been presenting beneficial effect for motor symptoms. However, non-motor symptoms and signs in PD have been accumulated growing attentions and its amelioration may also give beneficial effect for PD patients’ and their care givers’ quality of life. In this mini-review, I overviewed non-motor symptoms and signs in PD.展开更多
文摘Objective: In the manuscript titled “Liquid subcutaneous Levodopa-Carbidopa ND0612 effects on motor symptoms in individuals with Parkinson’s Disease: A systematic review and meta-analysis”, the objective was to conduct a systematic review with meta-analysis to investigate the effects ND0612 24-hour dosing regimen has on motor symptoms in individuals with Parkinson’s Disease (PD). Introduction: ND0612 is a novel minimally invasive continuous subcutaneous delivery system of liquid Levodopa-Carbidopa being investigated for the treatment of PD in individuals experiencing motor symptoms. Methods: A systematic literature search was conducted in PubMed, Cochrane, and EBSCO databases to identify randomized controlled trials investigating the effects of ND0612 on motor symptoms in individuals with PD. Outcomes included the Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and Part III scores. Methodological quality was assessed using the Cochrane Grading of Recommendations Assessment, Development, and Evaluation approach. Meta-analysis was performed using a random effects model with the DerSimonian and Laird method to estimate the effects of the ND0612 24-hour dosing regimen on UPDRS Part II and Part III scores. Results: Three studies were included in our review. There were statistically significant reductions in UPDRS Part II scores (mean difference (MD) −3.299;95% confidence interval (CI) −3.438, −3.159) and in UPDRS Part III scores (MD −12.695;95% CI −24.428, −0.962) in the ND0612 24-hour dosing regimen. Results were based on very low certainty of evidence. Conclusion: Based on very low certainty evidence, the ND0612 24-hour dosing regimen is effective at improving motor symptoms in individuals with PD. Our findings suggest that ND0612 is more effective at improving UPDRS Part II and Part III scores in individuals with PD than other pharmacological and non-pharmacological treatments, warranting further study.
文摘<strong>Background: </strong>Parkinson’s disease (PD) remains a challenge for neurologists, particularly in its advanced stages when non-motor symptoms become a burden for the patient. While motor symptoms may be satisfactorily controlled with levodopa therapy or continuous levodopa/carbidopa intestinal gel (LCIG) administration, autonomic, sleep and mental disorders are hard to treat. During the last years, researchers have shifted their interest more to non-motor symptoms, PD being now considered a complex multiorgan impairment. <strong>Objective:</strong> The aim of this study was to describe non-motor symptoms in 40 Romanian patients diagnosed with PD, under conventional and LCIG administration treatment. <strong>Methods: </strong>A cross-sectional observational study was conducted, consisting of two groups of 20 patients each: the first group comprised PD patients who received conventional Levodopa treatment, while the second group was formed of patients receiving LCIG therapy. Various data concerning patient’s age, gender, duration of illness, comorbidities, motor and non-motor symptoms were recorded. The data were processed in SPSS v.20. <strong>Results: </strong>Subjects under continuous LCIG administration, although showing amelioration of motor symptoms, complained more frequently of constipation, mental, and sleeping disorders (statistically significant). Regarding anosmia, orthostatic hypotension, hypersalivation, urinary incontinence and restless legs syndrome, no statistical significant difference was observed between the two groups (p > 0.05). <strong>Conclusion:</strong> Nowadays, more research is conducted on non-motor symptoms in PD patients, as therapeutic measures try to limit these burdens, in order to improve patient’s quality of life.
基金supported by the National Institutes of Health (R15-HD061022 and R15-HD061022-S1)the Faculty Development Fund of the School of Pharmacy and Health Professions,Creighton University in Omaha Nebraska,USA
文摘Parkinson＇s disease （PD） is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have dif- ferent rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.
基金This work was supported by Key Research and Development Program of Guangdong Province(2019B030335001)the Natural Science Foundation of China(31871070,82090031)+4 种基金Key R&D Program of Zhejiang Province(2020C03009)Science and Technology Program of Guangdong(2018B030334001)Funds for Creative Research Groups of China from the National Natural Science Foundation of China(81521062)Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2019PT310023)CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057).
文摘Parkinson’s disease(PD)is the second most common and fastest-growing neurodegenerative disorder.In recent years,it has been recognized that neurotransmitters other than dopamine and neuronal systems outside the basal ganglia are also related to PD pathogenesis.However,little is known about whether and how the caudal zona incerta(ZIc)regulates parkinsonian motor symptoms.Here,we showed that specific glutamatergic but not GABAergic ZIc^(VgluT2) neurons regulated these symptoms.ZIc^(VgluT2) neuronal activation induced time-locked parkinsonian motor symptoms.In mouse models of PD,the ZIc^(VgluT2) neurons were hyperactive and inhibition of their activity ameliorated the motor deficits.ZIc^(VgluT2) neurons monosynaptically projected to the substantia nigra pars reticulata.Incerta-nigral circuit activation induced parkinsonian motor symptoms.Together,our findings provide a direct link between the ZIc,its glutamatergic neurons,and parkinsonian motor symptoms for the first time,help to better understand the mechanisms of PD,and supply a new important potential therapeutic target for PD.
文摘Background Although the validity of non-motor symptoms screening questionnaire （NMSQuest） for Parkinson＇s disease has been verified in several recent researches, the specificity of the questionnaire is still in doubt. This study aimed to compare the non-motor symptoms （NMS） in Parkinson＇s disease （PD） with a medically ill control group. Methods In this study, the first comprehensive clinic-based NMS screening questionnaire for PD developed by the Parkinson＇s Disease Non-Motor Group （PDNMG） was used. Data from 90 PD patients and 270 sex-and age-matched control subjects, including stroke （n=90）, heart disease （n=-90） and diabetes （n=-90） were analyzed. Results Compared with control group, NMS was more common in PD; on an average, most PD patients reported more than 12 non-motor items. There was a correlation of total NMS score in PD patients with Hoehn ＆ Yahr Staging, but not with age, sex distribution, disease duration, or age at disease onset. Additionally, depression, constipation and impaired olfaction which occurred prior to the motor symptoms of PD were reported in this study. Conclusions NMS are more common in PD patients. There are some NMS that occurred at the preclinical stage of PD and might predict the onset of motor symptoms of PD patients.
基金the National Natural Science Foundation of China(81430022,91332107,81371407,81801267,31771174,82151303)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)Shanghai Municipal Education Commission(2017NKX001).
文摘Background:Tai Chi has been shown to improve motor symptoms in Parkinson’s disease(PD),but its long-term effects and the related mechanisms remain to be elucidated.In this study,we investigated the effects of long-term Tai Chi training on motor symptoms in PD and the underlying mechanisms.Methods:Ninety-five early-stage PD patients were enrolled and randomly divided into Tai Chi(n=32),brisk walk-ing(n=31)and no-exercise(n=32)groups.At baseline,6 months and 12 months during one-year intervention,all participants underwent motor symptom evaluation by Berg balance scale(BBS),Unified PD rating-scale(UPDRS),Timed Up and Go test(TUG)and 3D gait analysis,functional magnetic resonance imaging(fMRI),plasma cytokine and metabolomics analysis,and blood Huntingtin interaction protein 2(HIP2)mRNA level analysis.Longitudinal self-changes were calculated using repeated measures ANOVA.GEE(generalized estimating equations)was used to assess factors associated with the longitudinal data of rating scales.Switch rates were used for fMRI analysis.False discovery rate correction was used for multiple correction.Results:Participants in the Tai Chi group had better performance in BBS,UPDRS,TUG and step width.Besides,Tai Chi was advantageous over brisk walking in improving BBS and step width.The improved BBS was correlated with enhanced visual network function and downregulation of interleukin-1β.The improvements in UPDRS were asso-ciated with enhanced default mode network function,decreased L-malic acid and 3-phosphoglyceric acid,and increased adenosine and HIP2 mRNA levels.In addition,arginine biosynthesis,urea cycle,tricarboxylic acid cycle and beta oxidation of very-long-chain fatty acids were also improved by Tai Chi training.Conclusions:Long-term Tai Chi training improves motor function,especially gait and balance,in PD.The underlying mechanisms may include enhanced brain network function,reduced inflammation,improved amino acid metabolism,energy metabolism and neurotransmitter metabolism,and decreased vulnerability to dopaminergic degeneration.Trial registration This study has been registered at Chinese Clinical Trial Registry(Registration number:ChiCTR2000036036;Registration date:August 22,2020).
基金supported by intramural funding from the University of South Carolina McCausland Center for Brain Imaging
文摘Many studies have examined motor impairments using voxel-based lesion symptom mapping, but few are reported regarding the corresponding relationship between cerebral cortex injury and lower limb motor impairment analyzed using this technique. This study correlated neuro- nal injury in the cerebral cortex of 16 patients with chronic stroke based on a voxel-based lesion symptom mapping analysis. Neuronal injury in the corona radiata, caudate nucleus and putamen of patients with chronic stroke could predict walking speed. The behavioral measure scores were consistent with motor deficits expected after damage to the cortical motor system due to stroke. These findings suggest that voxel-based lesion symptom mapping may provide a more accurate prognosis of motor recovery from chronic stroke according to neuronal injury in cerebral motor cortex.
文摘Motor symptoms are cardinal clinical features of Parkinson’s disease (PD). Progress in drug therapy and rehabilitation has been presenting beneficial effect for motor symptoms. However, non-motor symptoms and signs in PD have been accumulated growing attentions and its amelioration may also give beneficial effect for PD patients’ and their care givers’ quality of life. In this mini-review, I overviewed non-motor symptoms and signs in PD.
