differential diagnosis.PSP presents a range of ocular abnormalities that have been suggested as optional tools for its early detection,apart from the principal characteristic of postural unsteadiness.Nonetheless,such ...differential diagnosis.PSP presents a range of ocular abnormalities that have been suggested as optional tools for its early detection,apart from the principal characteristic of postural unsteadiness.Nonetheless,such symptoms may be difficult to identify,particularly during the early onset stage of the disorder.It may also be problematic to recognize these symptoms for general practitioners who lack the required experience or physicians who are not specifically educated and proficient in ophthalmology or neurology.Main body:Thus,here,a methodical evaluation was carried out to identify seven oculomotor abnormalities occurring in PSP,comprising square wave jerks,the speed and range of saccades(slow saccades and vertical supranuclear gaze palsy),‘round the houses’sign,decreased blink rate,blepharospasm,and apraxia of eyelid opening.Inspections were conducted using direct visual observation.An approach to distinguish these signs during a bedside examination was also established.When presenting in a patient with parkinsonism or dementia,the existence of such ocular abnormalities could increase the risk of PSP.For the distinction between PSP and other parkinsonian disorders,these signs hold significant value for physicians.Conclusion:The authors urge all concerned physicians to check for such abnormalities with the naked eye in patients with parkinsonism.This method has advantages,including ease of application,reduced time-consumption,and requirement of minimal resources.It will also help physicians to conduct efficient diagnoses since many patients with PSP could intially present with ocular symptoms in busy outpatient clinics.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
目的:探讨进行性核上性麻痹(PSP)患者扩大的血管周围间隙(EPVS)的影像学特点及临床意义。方法:回顾性观察9名PSP患者、23名帕金森病(PD)患者及25名健康对照者的3.0T头MRI,在T2WI上分别计数半卵圆中心、基底节区及中脑的EPVS,分析各组不...目的:探讨进行性核上性麻痹(PSP)患者扩大的血管周围间隙(EPVS)的影像学特点及临床意义。方法:回顾性观察9名PSP患者、23名帕金森病(PD)患者及25名健康对照者的3.0T头MRI,在T2WI上分别计数半卵圆中心、基底节区及中脑的EPVS,分析各组不同部位EPVS的差异,并分析EPVS评分与Hoehn and Yahr(H&Y)分级和MMSE评分之间的相关性。结果:在半卵圆中心和基底节区层面,PSP组EPVS评分高于PD组和对照组(P<0.05)。PSP组患者H&Y分级与半卵圆中心(r_(S)=0.415,P=0.018)和基底节区(r_(S)=0.374,P=0.035)EPVS评分呈正相关;MMSE评分与半卵圆中心(r_(S)=-0.379,P=0.004)和基底节区(r_(S)=-0.336,P=0.011)EPVS评分呈负相关。结论:PSP患者的EPVS扩大更严重,并且与运动障碍和认知障碍相关,这可能成为PSP影像诊断及病程评估的一项客观指标。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The study has been funded by the Chulalongkorn Academic Advancement Fund into Its second Century Project of Chulalongkorn University(2300042200)a Center of Excellence grant from Chulalongkorn University(GCE 6100930004-1).
文摘differential diagnosis.PSP presents a range of ocular abnormalities that have been suggested as optional tools for its early detection,apart from the principal characteristic of postural unsteadiness.Nonetheless,such symptoms may be difficult to identify,particularly during the early onset stage of the disorder.It may also be problematic to recognize these symptoms for general practitioners who lack the required experience or physicians who are not specifically educated and proficient in ophthalmology or neurology.Main body:Thus,here,a methodical evaluation was carried out to identify seven oculomotor abnormalities occurring in PSP,comprising square wave jerks,the speed and range of saccades(slow saccades and vertical supranuclear gaze palsy),‘round the houses’sign,decreased blink rate,blepharospasm,and apraxia of eyelid opening.Inspections were conducted using direct visual observation.An approach to distinguish these signs during a bedside examination was also established.When presenting in a patient with parkinsonism or dementia,the existence of such ocular abnormalities could increase the risk of PSP.For the distinction between PSP and other parkinsonian disorders,these signs hold significant value for physicians.Conclusion:The authors urge all concerned physicians to check for such abnormalities with the naked eye in patients with parkinsonism.This method has advantages,including ease of application,reduced time-consumption,and requirement of minimal resources.It will also help physicians to conduct efficient diagnoses since many patients with PSP could intially present with ocular symptoms in busy outpatient clinics.
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.
文摘目的:探讨进行性核上性麻痹(PSP)患者扩大的血管周围间隙(EPVS)的影像学特点及临床意义。方法:回顾性观察9名PSP患者、23名帕金森病(PD)患者及25名健康对照者的3.0T头MRI,在T2WI上分别计数半卵圆中心、基底节区及中脑的EPVS,分析各组不同部位EPVS的差异,并分析EPVS评分与Hoehn and Yahr(H&Y)分级和MMSE评分之间的相关性。结果:在半卵圆中心和基底节区层面,PSP组EPVS评分高于PD组和对照组(P<0.05)。PSP组患者H&Y分级与半卵圆中心(r_(S)=0.415,P=0.018)和基底节区(r_(S)=0.374,P=0.035)EPVS评分呈正相关;MMSE评分与半卵圆中心(r_(S)=-0.379,P=0.004)和基底节区(r_(S)=-0.336,P=0.011)EPVS评分呈负相关。结论:PSP患者的EPVS扩大更严重,并且与运动障碍和认知障碍相关,这可能成为PSP影像诊断及病程评估的一项客观指标。
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.
