The role of substantia nigra sonography in the differentiation of Parkinson’s disease and multiple system atrophy

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.

How to spot ocular abnormalities in progressive supranuclear palsy?A practical review

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.

Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease

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.