Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these ...Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.展开更多
Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early di...Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.展开更多
BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is i...BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.展开更多
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
Background:Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction....Background:Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction.To distinguish MSA-P from IPD when the symptoms are relatively mild,we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status.Methods:Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study.We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3.Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing,Valsalva ratio (VR),and regression slope of systolic blood pressure (BP) in early phase Ⅱ (vagal baroreflex sensitivity) during Valsalva maneuver.Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT),sympathetic index 1,sympathetic index 3,early phase Ⅱ mean BP drop,and pulse pressure reduction rate.Additionally,we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients.Results:PRT was significantly different between the IPD and MSA-P groups (P =0.004) despite the similar BP drop during tilt.Cutoff value of PRT was 5.5 s (sensitivity,71.4%;specificity,72.7%).VR (r =-0.455,P =0.009) and BRSa (r =-0.356,P =0.036) demonstrated a significant correlation with UMSARS and H&Y scores.Conclusions:Among the cardiovascular autonomic indexes,PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD.Moreover,VR,and BRSa may be the optimal indexes in determining functional symptom severity.展开更多
目的系统评价血清神经丝轻链蛋白(neurofilament light chain protein,NfL)在神经退行性疾病及不同认知损害程度患者中的变化。方法计算机检索PubMed、Embase、Web of Science、中国知网、万方和中国生物医学文献库数据库,纳入阿尔茨海...目的系统评价血清神经丝轻链蛋白(neurofilament light chain protein,NfL)在神经退行性疾病及不同认知损害程度患者中的变化。方法计算机检索PubMed、Embase、Web of Science、中国知网、万方和中国生物医学文献库数据库,纳入阿尔茨海默病(Alzheimer's disease,AD)、帕金森病(Parkinson's disease,PD)、多系统萎缩(multiple system atrophy,MSA)、进行性核上性麻痹(progressive supranuclear palsy,PSP)患者和健康对照均有血清NfL值的队列或病例对照研究,检索时间为建库至2023年4月30日。使用纽卡斯尔-渥太华量表评价纳入研究的风险偏倚,采用RevMan 5.4软件统计分析暴露组与非暴露组间的血清NfL值差异,合并效应量采用标准均数差(standard mean difference,SMD)及95%可信区间(confidence interval,CI)表示。结果纳入43篇文献,共提取了62项对比研究。对PD、AD、MSA、PSP与各自健康对照组分组比较,四组分别纳入9项、24项、9项、8项研究。PD组[SMD=0.27,95%CI(0.17,0.36)]、AD组[SMD=0.97,95%CI(0.70,1.23)]、MSA组[SMD=1.51,95%CI(0.97,2.05)]、PSP组[SMD=1.54,95%CI(1.14,1.93)]血清NfL水平均高于各自健康对照组。对帕金森病认知正常(PD normal cognitive,PD-NC)与帕金森病痴呆(PD with dementia,PD-D)、阿尔茨海默病轻度认知减退(AD mild cognitive impairment,AD-MCI)与阿尔茨海默病痴呆(AD with dementia,AD-D)分组比较,两对比组分别纳入3项和9项研究,PD-D患者血清NfL水平高于PD-NC患者[SMD=0.92,95%CI(0.63,1.20)],AD-D患者血清NfL水平高于AD-MCI患者[SMD=0.61,95%CI(0.49,0.72)]。结论PD、AD、MSA、PSP患者血清NfL水平较健康人群升高,且认知损害程度越大,血清NfL水平越高,血清NfL可能是神经退行性疾病潜在的外周生物标志物,能够进一步反映认知水平的下降。展开更多
Background： Both Parkinson＇s disease （PD） and multiple system atrophy （MSA） have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism （...Background： Both Parkinson＇s disease （PD） and multiple system atrophy （MSA） have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism （MSA-P） resembles PD in the manifestation of prominent parkinsonism, Whether the amount of rapid eye movement （REM） sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods： This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder （RBD） prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram （EMG） activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results： No significant difference between MSA-P group and PD group had been tbund in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index （AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024） and higher tonic chin EMG density （34.02 [ 18.48, 57.18]% vs. 8.40 [3.11, 13.061%, P 〈 0.001 ） as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA ＋ RBD subgroup was higher than that in PD ＋ RBD subgroup （55.04 [26.81,69.62]% vs. 11.40 [8.51,20.411%, P 〈 0.001 ）. Furthermore, no evidence of any difference in tonic EMG density emerged between PD ＋ RBD and MSA - RBD subgroups （P 〉 0.05）. Both disease duration （P = 0.056） and AHI （P = 0.051） showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD ＋ RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P （[3 0.552, P 〈 0.001 ） and RBD （[3 = 0.433, P 〈 0.001 ） as predictors of higher tonic EMG density. Conclusion： Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.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
目的探讨颈部迷走神经横截面面积(CAS)对帕金森病(PD)的诊断价值。方法选择2019年10月至2022年10月郑州大学人民医院收治的30例PD患者为PD组,同期郑州大学人民医院收治的25例多系统萎缩(MSA)患者为MSA组,另选择同期于郑州大学人民医院...目的探讨颈部迷走神经横截面面积(CAS)对帕金森病(PD)的诊断价值。方法选择2019年10月至2022年10月郑州大学人民医院收治的30例PD患者为PD组,同期郑州大学人民医院收治的25例多系统萎缩(MSA)患者为MSA组,另选择同期于郑州大学人民医院体检健康者30人为健康对照组。采用高分辨率超声测量3组受试者的颈部迷走神经CAS,比较3组受试者颈部迷走神经CAS的差异;采用PD自主神经症状量表(SCOPA-AUT)评估3组受试者自主神经功能的受损程度,采用受试者操作特征(ROC)曲线分析颈部迷走神经CAS对PD的诊断价值。结果健康对照组、PD组受试者右侧颈部迷走神经CAS显著大于左侧(P<0.05);MSA组受试者双侧颈部迷走神经CAS比较差异无统计学意义(P>0.05)。PD组、MSA组受试者双侧颈部迷走神经CAS及平均CAS均显著小于健康对照组(P<0.01)。MSA组受试者右侧颈部迷走神经CAS显著小于PD组(P<0.05);MSA组受试者左侧颈部迷走神经CAS及平均CAS与PD组比较差异无统计学意义(P>0.05)。PD组、MSA组受试者SCOPA-AUT总分及胃肠道(GI)、心血管系统(CV)、泌尿系统(UR)、性功能(SX)评分显著高于健康对照组(P<0.01)。MSA组受试者的SCOPA-AUT总分及UR、SX评分显著高于PD组(P<0.05)。3组受试者的体温调节(TH)、瞳孔活动(PU)评分比较差异无统计学意义(P>0.05)。Pearson相关性分析显示,PD患者颈部迷走神经CAS与SCOPA-AUT总分及UR、TH、PU、SX评分均无相关性(r=-0.143、0.281、0.297、0.265、0.312,P>0.05),PD患者颈部迷走神经CAS与GI、CV评分呈负相关(r=-0.683、-0.373,P<0.05)。ROC曲线分析显示,颈部迷走神经诊断PD的曲线下面积为0.870(95%置信区间:0.773~0.966,P<0.05),临界值为3.064 mm 2,敏感度为96%,特异度为67%;颈部迷走神经CAS鉴别PD、MSA的线下面积为0.680(95%置信区间:0.537~0.823,P<0.05);当颈部迷走神经CAS<2.709 mm 2时诊断MSA的敏感度为68%,特异度为70%。结论颈部迷走神经CAS对诊断PD具有较高的临床价值,为提高PD的诊断率提供了新的思路。展开更多
基金the authors are supported by grants from Natural Science Foundation of China(81671244,81371200,and 81401042)a special fund from Key Laboratory of Neurodegenerative Disease,Ministry of Education(PXM2019_026283_000002)+1 种基金Beijing Municipal Science and Technology Commission(Z161100005116011,Z171100000117013)Beijing Municipal commission of Health and Family Planning(PXM2017_026283_000002).
文摘Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.
基金supported by the Italian Ministry of Health (’Ricerca Corrente’2020-2021)(to MT)。
文摘Multiple system atrophy is a sporadic,progressive,adult-onset,neurodegenerative disorder characte rized by autonomic dysfunction symptoms,parkinsonian features,and cerebellar signs in va rious combinations.An early diagnosis of multiple system atrophy is of utmost impo rtance for the proper prevention and management of its potentially fatal complications leading to the poor prognosis of these patients.The current diagnostic criteria incorporate several clinical red flags and magnetic resonance imaging marke rs supporting diagnosis of multiple system atrophy.Nonetheless,especially in the early disease stage,it can be challenging to differentiate multiple system atrophy from mimic disorders,in particular Parkinson’s disease.Electromyography of the external anal sphincter represents a useful neurophysiological tool for diffe rential diagnosis since it can provide indirect evidence of Onuf’s nucleus degeneration,which is a pathological hallmark of multiple system atrophy.However,the diagnostic value of external anal sphincter electromyography has been a matter of debate for three decades due to controve rsial reports in the literature.In this review,after a brief ove rview of the electrophysiological methodology,we first aimed to critically analyze the available knowledge on the diagnostic role of external anal sphincter electromyography.We discussed the conflicting evidence on the clinical correlations of neurogenic abnormalities found at external anal sphincter electro myography.Finally,we repo rted recent prognostic findings of a novel classification of electromyography patterns of the external anal sphincter that could pave the way toward the implementation of this neurophysiological technique for survival prediction in patients with multiple system atrophy.
基金Supported by National Natural Science Foundation of China,No.81771373Key Research and Development Plan of Zibo City,No.2019ZC010169 and No.2019ZC010166.
文摘BACKGROUND Multiple system atrophy(MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15(GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA.AIM To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson’s disease(PD) patients and healthy controls.METHODS A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzymelinked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysiswas used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD.RESULTS Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls(P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels(P = 0.043 and 0.000;respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients(cutoff: 470.42 pg/m L, sensitivity: 85.7%, specificity: 88.0%;cutoff: 1075.91 pg/m L, sensitivity:51.0%, specificity: 96.0%;respectively).CONCLUSION Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.
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Background:Differential diagnosis of idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) is challenging since they share clinical features with parkinsonism and autonomic dysfunction.To distinguish MSA-P from IPD when the symptoms are relatively mild,we investigated the usefulness of the quantitative fractionalized autonomic indexes and evaluated the correlations of autonomic test indexes and functional status.Methods:Thirty-six patients with parkinsonism (22 with IPD and 14 with MSA-P) in Soonchunhyang University Bucheon Hospital from February 2014 to June 2015 were prospectively enrolled in the study.We compared fractionalized autonomic indexes and composite autonomic scoring scale between patients with IPD and MSA-P with Hoehn and Yahr (H&Y) score ≤3.Parasympathetic indexes included expiratory/inspiratory ratio during deep breathing,Valsalva ratio (VR),and regression slope of systolic blood pressure (BP) in early phase Ⅱ (vagal baroreflex sensitivity) during Valsalva maneuver.Sympathetic adrenergic indexes were pressure recovery time (PRT) and adrenergic baroreflex sensitivity (BRSa) (BP decrement associated with phase 3 divided by the PRT),sympathetic index 1,sympathetic index 3,early phase Ⅱ mean BP drop,and pulse pressure reduction rate.Additionally,we compared the unified multiple system atrophy rating scale (UMSARS) and H&Y scores and the autonomic indexes in all patients.Results:PRT was significantly different between the IPD and MSA-P groups (P =0.004) despite the similar BP drop during tilt.Cutoff value of PRT was 5.5 s (sensitivity,71.4%;specificity,72.7%).VR (r =-0.455,P =0.009) and BRSa (r =-0.356,P =0.036) demonstrated a significant correlation with UMSARS and H&Y scores.Conclusions:Among the cardiovascular autonomic indexes,PRT can be a useful parameter in differentiating the early stage of MSA-P from that of IPD.Moreover,VR,and BRSa may be the optimal indexes in determining functional symptom severity.
文摘目的系统评价血清神经丝轻链蛋白(neurofilament light chain protein,NfL)在神经退行性疾病及不同认知损害程度患者中的变化。方法计算机检索PubMed、Embase、Web of Science、中国知网、万方和中国生物医学文献库数据库,纳入阿尔茨海默病(Alzheimer's disease,AD)、帕金森病(Parkinson's disease,PD)、多系统萎缩(multiple system atrophy,MSA)、进行性核上性麻痹(progressive supranuclear palsy,PSP)患者和健康对照均有血清NfL值的队列或病例对照研究,检索时间为建库至2023年4月30日。使用纽卡斯尔-渥太华量表评价纳入研究的风险偏倚,采用RevMan 5.4软件统计分析暴露组与非暴露组间的血清NfL值差异,合并效应量采用标准均数差(standard mean difference,SMD)及95%可信区间(confidence interval,CI)表示。结果纳入43篇文献,共提取了62项对比研究。对PD、AD、MSA、PSP与各自健康对照组分组比较,四组分别纳入9项、24项、9项、8项研究。PD组[SMD=0.27,95%CI(0.17,0.36)]、AD组[SMD=0.97,95%CI(0.70,1.23)]、MSA组[SMD=1.51,95%CI(0.97,2.05)]、PSP组[SMD=1.54,95%CI(1.14,1.93)]血清NfL水平均高于各自健康对照组。对帕金森病认知正常(PD normal cognitive,PD-NC)与帕金森病痴呆(PD with dementia,PD-D)、阿尔茨海默病轻度认知减退(AD mild cognitive impairment,AD-MCI)与阿尔茨海默病痴呆(AD with dementia,AD-D)分组比较,两对比组分别纳入3项和9项研究,PD-D患者血清NfL水平高于PD-NC患者[SMD=0.92,95%CI(0.63,1.20)],AD-D患者血清NfL水平高于AD-MCI患者[SMD=0.61,95%CI(0.49,0.72)]。结论PD、AD、MSA、PSP患者血清NfL水平较健康人群升高,且认知损害程度越大,血清NfL水平越高,血清NfL可能是神经退行性疾病潜在的外周生物标志物,能够进一步反映认知水平的下降。
文摘Background： Both Parkinson＇s disease （PD） and multiple system atrophy （MSA） have associated sleep disorders related to the underlying neurodegenerative pathology. Clinically, MSA with predominant parkinsonism （MSA-P） resembles PD in the manifestation of prominent parkinsonism, Whether the amount of rapid eye movement （REM） sleep without atonia could be a potential marker for differentiating MSA-P from PD has not been thoroughly investigated. This study aimed to examine whether sleep parameters could provide a method for differentiating MSA-P from PD. Methods： This study comprised 24 MSA-P patients and 30 PD patients, and they were of similar age, gender, and REM sleep behavior disorder （RBD） prevalence. All patients underwent clinical evaluation and one night of video-polysomnography recording. The tonic and phasic chin electromyogram （EMG） activity was manually quantified during REM sleep of each patient. We divided both groups in terms of whether they had RBD to make subgroup analysis. Results： No significant difference between MSA-P group and PD group had been tbund in clinical characteristics and sleep architecture. However, MSA-P patients had higher apnea-hypopnea index （AHI; 1.15 [0.00, 8.73]/h vs. 0.00 [0.00, 0.55]/h, P = 0.024） and higher tonic chin EMG density （34.02 [ 18.48, 57.18]% vs. 8.40 [3.11, 13.061%, P 〈 0.001 ） as compared to PD patients. Subgroup analysis found that tonic EMG density in MSA ＋ RBD subgroup was higher than that in PD ＋ RBD subgroup （55.04 [26.81,69.62]% vs. 11.40 [8.51,20.411%, P 〈 0.001 ）. Furthermore, no evidence of any difference in tonic EMG density emerged between PD ＋ RBD and MSA - RBD subgroups （P 〉 0.05）. Both disease duration （P = 0.056） and AHI （P = 0.051） showed no significant differences during subgroup analysis although there was a trend toward longer disease duration in PD ＋ RBD subgroup and higher AHI in MSA - RBD subgroup. Stepwise multiple linear regression analysis identified the presence of MSA-P （[3 0.552, P 〈 0.001 ） and RBD （[3 = 0.433, P 〈 0.001 ） as predictors of higher tonic EMG density. Conclusion： Tonic chin EMG density could be a potential marker for differentiating MSA-P from PD.
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.
文摘目的探讨颈部迷走神经横截面面积(CAS)对帕金森病(PD)的诊断价值。方法选择2019年10月至2022年10月郑州大学人民医院收治的30例PD患者为PD组,同期郑州大学人民医院收治的25例多系统萎缩(MSA)患者为MSA组,另选择同期于郑州大学人民医院体检健康者30人为健康对照组。采用高分辨率超声测量3组受试者的颈部迷走神经CAS,比较3组受试者颈部迷走神经CAS的差异;采用PD自主神经症状量表(SCOPA-AUT)评估3组受试者自主神经功能的受损程度,采用受试者操作特征(ROC)曲线分析颈部迷走神经CAS对PD的诊断价值。结果健康对照组、PD组受试者右侧颈部迷走神经CAS显著大于左侧(P<0.05);MSA组受试者双侧颈部迷走神经CAS比较差异无统计学意义(P>0.05)。PD组、MSA组受试者双侧颈部迷走神经CAS及平均CAS均显著小于健康对照组(P<0.01)。MSA组受试者右侧颈部迷走神经CAS显著小于PD组(P<0.05);MSA组受试者左侧颈部迷走神经CAS及平均CAS与PD组比较差异无统计学意义(P>0.05)。PD组、MSA组受试者SCOPA-AUT总分及胃肠道(GI)、心血管系统(CV)、泌尿系统(UR)、性功能(SX)评分显著高于健康对照组(P<0.01)。MSA组受试者的SCOPA-AUT总分及UR、SX评分显著高于PD组(P<0.05)。3组受试者的体温调节(TH)、瞳孔活动(PU)评分比较差异无统计学意义(P>0.05)。Pearson相关性分析显示,PD患者颈部迷走神经CAS与SCOPA-AUT总分及UR、TH、PU、SX评分均无相关性(r=-0.143、0.281、0.297、0.265、0.312,P>0.05),PD患者颈部迷走神经CAS与GI、CV评分呈负相关(r=-0.683、-0.373,P<0.05)。ROC曲线分析显示,颈部迷走神经诊断PD的曲线下面积为0.870(95%置信区间:0.773~0.966,P<0.05),临界值为3.064 mm 2,敏感度为96%,特异度为67%;颈部迷走神经CAS鉴别PD、MSA的线下面积为0.680(95%置信区间:0.537~0.823,P<0.05);当颈部迷走神经CAS<2.709 mm 2时诊断MSA的敏感度为68%,特异度为70%。结论颈部迷走神经CAS对诊断PD具有较高的临床价值,为提高PD的诊断率提供了新的思路。
