Background:The differential diagnosis of Parkinson’s disease(PD)and multiple system atrophy(MSA)remains a challenge,especially in the early stage.Here,we assessed the value of transcranial sonography(TCS)to discrimin...Background:The differential diagnosis of Parkinson’s disease(PD)and multiple system atrophy(MSA)remains a challenge,especially in the early stage.Here,we assessed the value of transcranial sonography(TCS)to discriminate non-tremor dominant(non-TD)PD from MSA with predominant parkinsonism(MSA-P).Methods:Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study.All the patients were followed up for at least 2 years to confirm the initial diagnosis.Patients with at least one substantia nigra(SN)echogenic size≥18 mm^(2) were classified as hyperechogenic,those with at least one SN echogenic size≥25 mm^(2) was defined as markedly hyperechogenic.Results:The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients(74.1%vs.38.4%,p<0.001).SN hyperechogenicity discriminated non-TD PD from MSA-P with sensitivity of 74.1%,specificity of 61.6%,and positive predictive value of 76.8%.If marked SN hyperechogenicity was used as the cutoff value(≥25 mm^(2)),the sensitivity decreased to 46.3%,but the specificity and positive predictive value increased to 80.2 and 80.0%.Additionally,in those patients with SN hyperechogenicity,positive correlation between SN hyperechogenicity area and disease duration was found in non-TD PD rather than in MSA-P patients.In this context,among early-stage patients with disease duration≤3 years,the sensitivity,specificity and positive predictive value of SN hyperechogenicity further declined to 69.8%,52.2%,and 66.7%,respectively.Conclusions:TCS could help discriminate non-TD PD from MSA-P in a certain extent,but the limitation was also obvious with relatively low specificity,especially in the early stage.展开更多
What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-mo...What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major pathological hallmark of all PS consists of a non-physiological detrimental accumulation of protein aggregates which appear intracellularly in neurons and glial cells but also in the extracellular space (Wong and Krainc, 2017). Depending on the pathogenic protein, PS can be divided into synucleinopathies, characterized by aggregation of the protein alpha-Synuclein (aSyn), and tauopathies, characterized by aggregation of the protein Tau (Levin et al., 2016;Poewe et al., 2017). Clinical syndromes of synucleinopathies include Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies, and tauopathies include progressive supranuclear palsy (PSP) and corticobasal degeneration.展开更多
目的探讨MRI T_(2)WI壳核裂隙征以及壳核扩散加权低信号征、脑桥萎缩、桥臂萎缩在诊断P型多系统萎缩(Parkinsonism type of MSA,MSA-P)中的作用。方法选取2014-09至2019-07就诊于解放军总医院第六医学中心神经疑难疾病会诊中心的86例MS...目的探讨MRI T_(2)WI壳核裂隙征以及壳核扩散加权低信号征、脑桥萎缩、桥臂萎缩在诊断P型多系统萎缩(Parkinsonism type of MSA,MSA-P)中的作用。方法选取2014-09至2019-07就诊于解放军总医院第六医学中心神经疑难疾病会诊中心的86例MSA患者中诊断为MSA-P型的患者20例,并从影像储存与传输系统(picture achiving and communications system,PACS)上选取年龄性别匹配的健康对照组20例。对MSA-P型患者和健康成人的头颅常规MRI扫描序列,包括轴位及矢状位T_(2)加权,轴位T_(1)加权及弥散加权成像序列进行影像学征象分析。对两组患者的脑桥、桥臂萎缩,及壳核扩散加权低信号征,壳核背外侧裂隙征进行评价。结果20例MSA-P患者中,T_(2)加权像成像裂隙征70%(14/20),壳核扩散加权低信号征90%(18/20);脑桥萎缩30%(6/20),单侧或双侧桥臂萎缩40%(8/20)。MSA-P型患者组的T_(2)加权像成像裂隙征及壳核扩散加权低信号征与健康对照组对比,差异有统计学意义(P<0.01)。结论MSA-P患者T_(2)加权像成像裂隙征及壳核扩散加权低信号征阳性率明显高于桥臂及脑桥萎缩阳性率,是诊断P型多系统萎缩的主要征象,具有较高的临床诊断价值。展开更多
In the clinic,the diagnosis of Parkinson’s disease(PD)largely depends on clinicians’experience.When the diagnosis is made,approximately 80%of dopaminergic cells in the substantia nigra(SN)have been lost.Additionally...In the clinic,the diagnosis of Parkinson’s disease(PD)largely depends on clinicians’experience.When the diagnosis is made,approximately 80%of dopaminergic cells in the substantia nigra(SN)have been lost.Additionally,it is rather challenging to differentiate PD from atypical parkinsonian disorders(APD).Clinially-available 3T conventional MRI contributes little to solve these problems.The pathologic alterations of parkinsonism show abnormal brain iron deposition,and therefore susceptibility-weighted imaging(SWI),which is sensitive to iron concentration,has been applied to find iron-related lesions for the diagnosis and differentiation of PD in recent decades.Until now,the majority of research has revealed that in SWI the signal intensity changes in deep brain nuclei,such as the SN,the putamen(PUT),the globus pallidus(GP),the thalamus(TH),the red nucleus(RN)and the caudate nucleus(CN),thereby raising the possibility of early diagnosis and differentiation.Furthermore,the signal changes in SN,PUT and TH sub-regions may settle the issues with higher accuracy.In this article,we review the brain iron deposition of PD,MSA-P and PSP in SWI in the hope of exhibiting a profile of SWI features in PD,MSA and PSP and its clinical values.展开更多
Background There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease(PD).Cerebrospinal fluid(CSF)has been a successful biofluid for finding neurodegenerative biomarkers,and modern highly ...Background There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease(PD).Cerebrospinal fluid(CSF)has been a successful biofluid for finding neurodegenerative biomarkers,and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies.Using a large-scale multiplex proximity extension assay(PEA)approach,we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders(APD).Methods CSF from patients with PD,corticobasal syndrome(CBS),progressive supranuclear palsy(PSP),multiple system atrophy and controls,were analysed with Olink PEA panels.Three cohorts were used in this study,comprising 192,88 and 36 cases,respectively.All samples were run on the Cardiovascular II,Oncology II and Metabolism PEA panels.Results Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts,respectively,compared to controls.Among them,6 proteins were changed in both cohorts.Midkine(MK)was increased in PD with the strongest effect size and results were validated with ELISA.Another most increased protein in PD,DOPA decarboxylase(DDC),which catalyses the decarboxylation of DOPA(L-3,4-dihydroxyphenylalanine)to dopamine,was strongly correlated with dopaminergic treatment.Moreover,Kallikrein 10 was specifically changed in APD compared with both PD and controls,but unchanged between PD and controls.Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts.Conclusions Using the large-scale PEA approach,we have identified potential novel PD diagnostic biomarkers,most notably MK and DDC,in the CSF of PD patients.展开更多
基金This study was supported by Natural Science Fund of China(No.81430022,81371407,81771374)Innovation Program of Shanghai Municipal Education Commission(2017–01–07-00-01-E00046)Natural Science Foundation of Science and Technology of Shanghai(No.15ZR1426700).
文摘Background:The differential diagnosis of Parkinson’s disease(PD)and multiple system atrophy(MSA)remains a challenge,especially in the early stage.Here,we assessed the value of transcranial sonography(TCS)to discriminate non-tremor dominant(non-TD)PD from MSA with predominant parkinsonism(MSA-P).Methods:Eighty-six MSA-P patients and 147 age and gender-matched non-TD PD patients who had appropriate temporal acoustic bone windows were included in this study.All the patients were followed up for at least 2 years to confirm the initial diagnosis.Patients with at least one substantia nigra(SN)echogenic size≥18 mm^(2) were classified as hyperechogenic,those with at least one SN echogenic size≥25 mm^(2) was defined as markedly hyperechogenic.Results:The frequency of SN hyperechogenicity in non-TD PD patients was significantly higher than that in MSA-P patients(74.1%vs.38.4%,p<0.001).SN hyperechogenicity discriminated non-TD PD from MSA-P with sensitivity of 74.1%,specificity of 61.6%,and positive predictive value of 76.8%.If marked SN hyperechogenicity was used as the cutoff value(≥25 mm^(2)),the sensitivity decreased to 46.3%,but the specificity and positive predictive value increased to 80.2 and 80.0%.Additionally,in those patients with SN hyperechogenicity,positive correlation between SN hyperechogenicity area and disease duration was found in non-TD PD rather than in MSA-P patients.In this context,among early-stage patients with disease duration≤3 years,the sensitivity,specificity and positive predictive value of SN hyperechogenicity further declined to 69.8%,52.2%,and 66.7%,respectively.Conclusions:TCS could help discriminate non-TD PD from MSA-P in a certain extent,but the limitation was also obvious with relatively low specificity,especially in the early stage.
文摘What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major pathological hallmark of all PS consists of a non-physiological detrimental accumulation of protein aggregates which appear intracellularly in neurons and glial cells but also in the extracellular space (Wong and Krainc, 2017). Depending on the pathogenic protein, PS can be divided into synucleinopathies, characterized by aggregation of the protein alpha-Synuclein (aSyn), and tauopathies, characterized by aggregation of the protein Tau (Levin et al., 2016;Poewe et al., 2017). Clinical syndromes of synucleinopathies include Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies, and tauopathies include progressive supranuclear palsy (PSP) and corticobasal degeneration.
文摘目的探讨MRI T_(2)WI壳核裂隙征以及壳核扩散加权低信号征、脑桥萎缩、桥臂萎缩在诊断P型多系统萎缩(Parkinsonism type of MSA,MSA-P)中的作用。方法选取2014-09至2019-07就诊于解放军总医院第六医学中心神经疑难疾病会诊中心的86例MSA患者中诊断为MSA-P型的患者20例,并从影像储存与传输系统(picture achiving and communications system,PACS)上选取年龄性别匹配的健康对照组20例。对MSA-P型患者和健康成人的头颅常规MRI扫描序列,包括轴位及矢状位T_(2)加权,轴位T_(1)加权及弥散加权成像序列进行影像学征象分析。对两组患者的脑桥、桥臂萎缩,及壳核扩散加权低信号征,壳核背外侧裂隙征进行评价。结果20例MSA-P患者中,T_(2)加权像成像裂隙征70%(14/20),壳核扩散加权低信号征90%(18/20);脑桥萎缩30%(6/20),单侧或双侧桥臂萎缩40%(8/20)。MSA-P型患者组的T_(2)加权像成像裂隙征及壳核扩散加权低信号征与健康对照组对比,差异有统计学意义(P<0.01)。结论MSA-P患者T_(2)加权像成像裂隙征及壳核扩散加权低信号征阳性率明显高于桥臂及脑桥萎缩阳性率,是诊断P型多系统萎缩的主要征象,具有较高的临床诊断价值。
基金This work was funded by China National Nature Science Fund(No.81371421).
文摘In the clinic,the diagnosis of Parkinson’s disease(PD)largely depends on clinicians’experience.When the diagnosis is made,approximately 80%of dopaminergic cells in the substantia nigra(SN)have been lost.Additionally,it is rather challenging to differentiate PD from atypical parkinsonian disorders(APD).Clinially-available 3T conventional MRI contributes little to solve these problems.The pathologic alterations of parkinsonism show abnormal brain iron deposition,and therefore susceptibility-weighted imaging(SWI),which is sensitive to iron concentration,has been applied to find iron-related lesions for the diagnosis and differentiation of PD in recent decades.Until now,the majority of research has revealed that in SWI the signal intensity changes in deep brain nuclei,such as the SN,the putamen(PUT),the globus pallidus(GP),the thalamus(TH),the red nucleus(RN)and the caudate nucleus(CN),thereby raising the possibility of early diagnosis and differentiation.Furthermore,the signal changes in SN,PUT and TH sub-regions may settle the issues with higher accuracy.In this article,we review the brain iron deposition of PD,MSA-P and PSP in SWI in the hope of exhibiting a profile of SWI features in PD,MSA and PSP and its clinical values.
基金Open access funding provided by Karolinska Institutesupported by Karin and Sten Mörtstedt CBD Solutions AB,the Swedish Parkinson fund,the ALF program of the Stockholm Stockholm City,Lexa/Nordstjernan,Knut and Alice Wallenberg Foundation,and Van Geest Foundation.PS is a Wallenberg Clinical Scholar.
文摘Background There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease(PD).Cerebrospinal fluid(CSF)has been a successful biofluid for finding neurodegenerative biomarkers,and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies.Using a large-scale multiplex proximity extension assay(PEA)approach,we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders(APD).Methods CSF from patients with PD,corticobasal syndrome(CBS),progressive supranuclear palsy(PSP),multiple system atrophy and controls,were analysed with Olink PEA panels.Three cohorts were used in this study,comprising 192,88 and 36 cases,respectively.All samples were run on the Cardiovascular II,Oncology II and Metabolism PEA panels.Results Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts,respectively,compared to controls.Among them,6 proteins were changed in both cohorts.Midkine(MK)was increased in PD with the strongest effect size and results were validated with ELISA.Another most increased protein in PD,DOPA decarboxylase(DDC),which catalyses the decarboxylation of DOPA(L-3,4-dihydroxyphenylalanine)to dopamine,was strongly correlated with dopaminergic treatment.Moreover,Kallikrein 10 was specifically changed in APD compared with both PD and controls,but unchanged between PD and controls.Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts.Conclusions Using the large-scale PEA approach,we have identified potential novel PD diagnostic biomarkers,most notably MK and DDC,in the CSF of PD patients.
