Transcranial sonography in differential diagnosis of Parkinson disease and other movement disorders

Background:Reports evaluating the efficacy of transcranial sonography(TCS)for the differential diagnosis of Parkinson disease(PD)and other movement disorders in China are scarce.Therefore,this study aimed to assess the application of TCS for the differential diagnosis of PD,multiple system atrophy(MSA),progressive supranuclear palsy(PSP),and essential tremor(ET)in Chinese individuals.Methods:From 2017 to 2019,500 inpatients treated at the Department of Dyskinesia,Beijing Tiantan Hospital,Capital Medical University underwent routine transcranial ultrasound examination.The cross-sections at the midbrain and thalamus levels were scanned,and the incidence rates of substantia nigra(SN)positivity and the incidence rates of lenticular hyperechoic area were recorded.The echo of the SN was manually measured.Results:Of the 500 patients,125 were excluded due to poor signal in temporal window sound transmission.Among the 375 individuals with good temporal window sound transmission,200 were diagnosed with PD,90 with ET,50 with MSA,and 35 with PSP.The incidence rates of SN positivity differed significantly among the four patient groups(χ^(2)=121.061,P<0.001).Between-group comparisons were performed,and the PD group showed a higher SN positivity rate than the ET(χ^(2)=94.898,P<0.017),MSA(χ^(2)=57.619,P<0.017),and PSP(χ^(2)=37.687,P<0.017)groups.SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases,collectively or individually.The incidences of lenticular hyperechoic area significantly differed among the four patient groups(χ^(2)=38.904,P<0.001).Next,between-group comparisons were performed.The lenticular hyperechoic area was higher in the PD group than in the ET(χ^(2)=6.714,P<0.017)and MSA(χ^(2)=18.680,P<0.017)groups but lower than that in the PSP group(χ^(2)=0.679,P>0.017).Conclusion:SN positivity could effectively differentiate PD from ET,PSP,and MSA in a Chinese population.

Comparison of detection results of hypoxic-ischemic encephalopathy at different degrees in infant patients between brain electrical activity mapping, transcranial Doppler sonography and computer tomography examinations

BACKGROUND： It has been proved that brain electrical activity mapping （BEAM） and transcranial Doppler （TCD） detection can reflect the function of brain cell and its diseased degree of infant patients with moderate to severe hypoxic-ischemic encephalopathy （HIE）. OBJECTIVE： To observe the abnormal results of HIE at different degrees detected with BEAM and TCD in infant patients, and compare the detection results at the same time point between BEAM, TCD and computer tomography （CT） examinations. DESIGN ： Contrast observation SETTING： Departments of Neuro-electrophysiology and Pediatrics, Second Affiliated Hospital of Qiqihar Medical College. PARTICIPANTS： Totally 416 infant patients with HIE who received treatment in the Department of Newborn Infants, Second Affiliated Hospital of Qiqihar Medical College during January 2001 and December 2005. The infant patients, 278 male and 138 female, were at embryonic 37 to 42 weeks and weighing 2.0 to 4.1 kg, and they were diagnosed with CT and met the diagnostic criteria of HIE of newborn infants compiled by Department of Neonatology, Pediatric Academy, Chinese Medical Association. According to diagnostic criteria, 130 patients were mild abnormal, 196 moderate abnormal and 90 severe abnormal. The relatives of all the infant patients were informed of the experiment. METHOOS： BEAM and TCD examinations were performed in the involved 416 infant patients with HIE at different degrees with DYD2000 16-channel BEAM instrument and EME-2000 ultrasonograph before preliminary diagnosis treatment （within 1 month after birth） and 1,3,6,12 and 24 months after birth, and detected results were compared between BEAM, TCD and CT examinations. MAIN OUTCOME MEASURES： Comparison of detection results of HIE at different time points in infant patients between BEAM. TCD and CT examinations. RESULTS： All the 416 infant patients with HIE participated in the result analysis. （1） Comparison of the detected results in infant patients with mild HIE at different time points after birth between BEAM, TCD and CT examinations： BEAM examination showed that the recovery was delayed, and the abnormal rate of BEAM examination was significantly higher than that of CT examination 1 and 3 months after birth [55.4%（72/130）vs. 17.0% （22/130 ）,x^2=41.66 ;29.2% （ 38/130 ） vs. 6.2% （ 8/130 ）, x^2=23.77, P 〈 0.01 ], exceptional patients had mild abnormality and reached the normal level in about 6 months. TCD examination showed that the disease condition significantly improved and infant patients with HIE basically recovered 1 or 2 months after birth, while CT examination showed that infant patients recovered 3 or 4 months after birth. （2） Comparison of detection results of infant patients with moderate HIE at different time points between BEAM, TCD and CT examinations： The abnormal rate of BEAM examination was significantly higher than that of CT examination 1,3,6 and 12 months after birth [90.8% （178/196）,78.6% （154/196）,x^2=4.32,P 〈 0.05;64.3% （126/196）,43.9% （86/196） ,x^2=16.44 ;44.9% （88/196） ,22.4% （44/196）,x^2=22.11 ;21.4% （42/196）, 10.2% （20/196）,x^2=9.27, P 〈 0.01]. BEAM examination showed that there was still one patient who did not completely recovered in the 24^th month due to the relatives of infant patients did not combine the treatment,. TCD examination showed that the abnormal rate was 23.1%（30/196）in the 1^st month after birth, and all the patients recovered to the normal in the 3^rd month after birth, while CT examination showed that mild abnormality still existed in the 24^th month after birth （1.0% ,2/196）. （3） Comparison of detection results of infant patients with severe HIE at different time points between BEAM, TCD and CT examinations： The abnormal rate of BEAM examination was significantly higher than that of CT examination in the 1^st, 3^rd, 6^th and 12^th months after birth[86.7% （78/90）,44.4% （40/90）,x^2=35.53;62.2% （56/90）,31.1% （28/90）,x^2=17.51 ;37.8% （34/90）,6.7% （6/90）, x^2=27.14, P 〈 0.01]. BEAM examination showed that mild abnormality still existed in 4 infant patients in the 24^th month after birth. TCD examination showed that the abnormal rate was 11.1% （10/90） in the 3^rd month after birth, and all the infant patients recovered in the 6^th month after birth. CT examination showed that the abnormal rate was 6.7%（6/90） in the 12^th month after birth, and all of infant patients recovered to the normal in the 24^th month after birth.CONCLUSION ： BEAM is the direct index to detect brain function of infant patients with HIE, and positive reaction is still very sensitive in the tracking detection of convalescent period. The positive rate of morphological reaction in CT examination is superior to that in TCD examination, and the positive rate is very high in the acute period of HIE in examination.

Compromised cerebrovascular modulation in chronic anxiety:evidence from cerebral blood flow velocity measured by transcranial Doppler sonography

Objective Cerebral autoregulation （CA） is the mechanism by which constant cerebral blood flow is maintained despite changes in cerebral perfusion pressure. CA can be evaluated by dynamic monitoring of cerebral blood flow velocity （CBFV） with transcranial Doppler sonography （TCD）. The present study aimed to explore CA in chronic anxiety. Methods Subjects with Hamilton anxiety scale scores 〉14 were enrolled and the dynamic changes of CBFV in response to an orthostatic challenge were investigated using TCD. Results In both the anxious and the healthy subjects, the mean CBFV was significantly lower in the upright position than when supine. However, the CBFV changes from supine to upright differed between the anxious and the healthy groups. Anxious subjects showed more pronounced decreases in CBFV with abrupt standing. Conclusion Our results indicate that cerebrovascular modulation is compromised in chronic anxiety; anxious subjects have some insufficiency in maintaining cerebral perfusion after postural change. Given the fact that anxiety and impaired CA are associated with cardiovascular disease, early ascertainment of compromised cerebrovascular modulation using TCD might suggest interventional therapies in the anxious population, and improve the primary prevention of cardiovascular disease.

Transcranial Sonographic Alterations of Substantia Nigra and Third Ventricle in Parkinson＆#39;s Disease with or without Dementia

Background： Numerous studies have demonstrated that patients with Parkinson＆#39;s disease （PD） have a higher prevalence of substantia nigra （SN） hyperechogenicity compared with controls. Our aim was to explore the neuroimaging characteristics of transcranial sonography （TCS） of patients with PD and those with PD with dementia （PDD）. The correlation between the echogenicity of the SN and clinical symptoms in Chinese patients with PDD was also assessed. Methods： The ratios of SN hyperechogenicity （SN＋）, maximum sizes of SN＋, and widths of third ventricle （TV） were measured using TCS for all the recruited patients. Data were analyzed using one-way analysis of variance, rank-sum test, Chi-square test, and receiver-operating characteristic （ROC） curve analysis. Results： The final statistical analysis included 46 PDD patients, 52 PD patients, and 40 controls. There were no significant differences in ratios of SN＋ and maximum sizes of SN＋ between PDD and PD groups （P 〉 0.05）. TV widths were significantly larger in PDD group （7.1± 1.9 mm） than in PD group （6.0± 2.0 mm） and controls （5.9 ± 1.5 mm, P 〈 0.05）; however, the ratios of enlarged TV did not differ among the three groups （P = 0.059）. When cutoff value was set at 6.8 mm, the TV width had a relatively high sensitivity and specificity in discriminating between PDD and PD groups （P = 0.030） and between PDD group and controls （P = 0.003）, based on ROC curve analysis. In PDD patients, SN＋ was more frequently detected in akinetic-rigid subgroup, and patients with SN＋ showed significantly higher Hoehn and Yahr stage and Nonmotor Symptoms Questionnaire scores （P 〈 0.05）. Conclusions： Compared to Chinese patients with PD, patients with PDD had a wider TV, altered SN sonographic features, and more severe clinical symptoms. Our findings suggest that TCS can be used to assess brain atrophy in PD and may be useful in discriminating between PD with and without dementia.

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.

Combination of olfactory test and substantia nigra transcranial sonopraphy in the differential diagnosis of Parkinson’s disease:a pilot study from China

Objectives:Both hyposmia and substania nigra(SN)hyperechogenicity on trascranial sonography(TCS)were risk markers for idiopathic Parkinson’s disease(PD),which was beneficial to the differential diagnosis of the disease.However,each of their single diagnostic value is often limited.The purpose of present study was to explore whether the combination of olfactory test and TCS of SN could enhance the differential diagnostic power in Chinese patients with PD.Methods:Thirty-seven patients with PD and twenty-six patients with essential tremor(ET)were evaluated on 16-item odor identification test from extended version of sniffin’sticks and TCS of SN.The frequency of hyposmia and SN hyperechogenicity in each group was compared.The sensitivity,specificity,positive predictive value(PPV)and negative predictive value(NPV)of the two clinical biomarkers were analyzed.Results:The frequency of hyposmia in patients with PD was significantly higher than in patients with ET(62.2%VS.3.8%,P=0.000).The frequency of SN hyperechogenicity in patients with PD was significantly higher than in ET subjects(48.6%VS.15.4%,P=0.006).The combination of hyposmia and SN hyperechogenicity(if either one or both present)discriminated patients with PD from ET with a sensitivity of 78.4%and 29.7%,specificity of 80.8%and 100%,PPV of 85.3%and 100%,and NPV of 72.4%and 50.0%,respectively.Conclusions:Our preliminary data suggested that the combination of hyposmia and SN hyperechogenicity could improve the diagnostic potential for discriminating Chinese patients with PD from ET.

Effect of acupuncture at Lieque(列缺LU 7) on vertebral-basilar artery hemodynamics in patients with cervical vertigo

Objective To explore the therapeutic efficacy and mechanism of acupuncture at Lieque （列缺 LU 7） in treatment of cervical vertigo （CV）. Methods Forty CV patients met the inclusion criteria were enrolled and treated with acupuncture at bilateral LU 7 points, once daily with 10 times as a course. The changes of blood flow velocity in bilateral vertebral artery and basilar artery were observed through transcranial doppler sonography （TCD） before treatment, after deqi with acupuncture and after a course of treatment, respectively. The scores and therapeutic efficacy on clinical symptoms were assessed according to CV symptoms and the functional assessment scale as well as the Criteria-for Diagnosis and Curative Effect in TCM Syndromes before treatment and after a course of treatment. Results Before treatment, after deqi and after a course of treatment, the blood flow velocity of basilar artery （BA）, left vertebral artery （LVA） and right vertebral artery （RVA） in 22 patients with a decreased blood flow velocity were respectively 23.20±4.84 vs 26.30 ± 4.17 vs 29.20 ± 4.20 （mm/s, BA）, 21.65 ± 3.62 vs 24.20 ± 2.89 vs 26.40 ± 3.62 （mm/s, LVA） and 21.90±3.04 vs 24.25±3.01 vs 26.50_±3.95 （mm/s, RVA）, while in 18 patients with an increased blood flow velocity were respectively 39.94 ± 8.24 vs 35.17 ± 4.84 vs 32.06 ± 3.49 （mm/s, BA）, 41.83 ± 5.64 vs 37.28 ± 2.32 vs 35.61 ± 2.09 （mm/s, LVA） and 37.11 ± 9.83 vs 32.22 ± 6.13 vs 28.11 ± 4.12 （mm/s, RVA）. Except that the difference of blood flow velocity of RVA was not significant in patients with an increased blood flow velocity before treatment and after deqi （P 〉 0.05）, the Vm of all vessels in 40 patients was improved after deqi with acupuncture and a course of treatment （P〈0.01, P〈0.05）. According to CV symptoms and the functional assessment scale, before treatment and after a course of treatment, the scores were 15.68 ± 5.35 and 26.30 ± 3.76, respectively, indicating that after a course of treatment, the symptoms were significantly improved （P 〈 0.01）. According to the Criteria for Diagnosis and Curative E.f]ect in TCM Syndromes, after a course of treatment, the total effective rate was 100% （40/40） and the cured rate was 55.0% （22/40）. Conclusion Acupuncture at LU 7 not only improves the blood supply of vertebral-basilar artery in CV patients, but also has a significant curative effect on improving the clinical symptoms.

Imaging biomarkers in Parkinson’s disease and Parkinsonian syndromes:current and emerging concepts

Two centuries ago in 1817,James Parkinson provided the first medical description of Parkinson’s disease,later refined by Jean-Martin Charcot in the mid-to-late 19th century to include the atypical parkinsonian variants(also termed,Parkinson-plus syndromes).Today,Parkinson’s disease represents the second most common neurodegenerative disorder with an estimated global prevalence of over 10 million.Conversely,atypical parkinsonian syndromes encompass a group of relatively heterogeneous disorders that may share some clinical features with Parkinson’s disease,but are uncommon distinct clinicopathological diseases.Decades of scientific advancements have vastly improved our understanding of these disorders,including improvements in in vivo imaging for biomarker identification.Multimodal imaging for the visualization of structural and functional brain changes is especially important,as it allows a‘window’into the underlying pathophysiological abnormalities.In this article,we first present an overview of the cardinal clinical and neuropathological features of,1)synucleinopathies:Parkinson’s disease and other Lewy body spectrum disorders,as well as multiple system atrophy,and 2)tauopathies:progressive supranuclear palsy,and corticobasal degeneration.A comprehensive presentation of wellestablished and emerging imaging biomarkers for each disorder are then discussed.Biomarkers for the following imaging modalities are reviewed:1)structural magnetic resonance imaging(MRI)using T1,T2,and susceptibilityweighted sequences for volumetric and voxel-based morphometric analyses,as well as MRI derived visual signatures,2)diffusion tensor MRI for the assessment of white matter tract injury and microstructural integrity,3)proton magnetic resonance spectroscopy for quantifying proton-containing brain metabolites,4)single photon emission computed tomography for the evaluation of nigrostriatal integrity(as assessed by presynaptic dopamine transporters and postsynaptic dopamine D2 receptors),and cerebral perfusion,5)positron emission tomography for gauging nigrostriatal functions,glucose metabolism,amyloid and tau molecular imaging,as well as neuroinflammation,6)myocardial scintigraphy for dysautonomia,and 7)transcranial sonography for measuring substantia nigra and lentiform nucleus echogenicity.Imaging biomarkers,using the‘multimodal approach’,may aid in making early,accurate and objective diagnostic decisions,highlight neuroanatomical and pathophysiological mechanisms,as well as assist in evaluating disease progression and therapeutic responses to drugs in clinical trials.

Sonographic Alteration of Basal Ganglia in Different Forms of Primary Focal Dystonia： A Cross-sectional Study

Background：Few studies have addressed whether abnormalities in the lenticular nucleus （LN） are characteristic transcranial sonography （TCS） echo features in patients with primary dystonia.This study aimed to explore alterations in the basal ganglia in different forms of primary focal dystonia.Methods：A cross-sectional observational study was performed between December 2013 and December 20 1 4 in 80 patients with different forms of primary focal dystonia and 55 neurologically normal control subjects.TCS was performed in patients and control subjects.Multiple comparisons of multiple rates were used to compare LN hyperechogenicity ratios between control and patient groups.Results：Thirteen individuals were excluded due to poor temporal bone windows,and two subjects were excluded due to disagreement in evaluation by sonologists.Totally,70 patients （cervical dystonia,n =30;blepharospasm,n =30;oromandibular dystonia,n =10） and 50 normal controls were included in the final analysis.LN hyperechogenicity was observed in 51% （36/70） of patients with primary focal dystonia,compared with 12% （6/50） of controls （P 〈 0.001）.Substantia nigra hyperechogenicity did not differ between the two groups.LN hyperechogenicity was observed in 73% （22/30） of patients with cervical dystonia,a greater prevalence than in patients withblepharospasm （33%,10/30,P =0.002） and oromandibular dystonia （40%,4/10,P =0.126）.LN hyperechogenicity was more frequently observed in patients with cervical dystonia compared with controls （73% vs.12%,P 〈 0.001）;however,no significant difference was detected in patients with blepharospasm （33% vs.12%,P =0.021） or oromandibular dystonia （40% vs.12%,P =0.088）.Conclusions：LN hyperechogenicity is more frequently observed in patients with primary focal dystonia than in controls.It does not appear to be a characteristic TCS echo feature in patients with blepharospasm or oromandibular dystonia.

Primary study on imaging in transient ischemic attacks

Background Although transient ischemic attacks （TIA） is a clinical diagnosis, imaging findings are important for its diagnosis and treatment. This study evaluated the value and limitations of conventional CT, CT cerebral perfusion imaging and transcranial Doppler sonography （TCD） in patients with TIA. Methods Conventional CT, CT cerebral perfusion imaging and TCD were performed in 20 patients with TIA. After regular CT examination, d-0-second dynamic scans were performed on selected slice, while 40 ml of nonionic contrast materials was bolus-injected through antecubital vein with power injector. These dynamic images were processed with the perfusion software package on workstation. Cerebral blood flow （CBF） and time to peak （3~FP） were measured in specific regions of the brain. TCD was also performed in 20 patients with TIA. Comparative analysis was made on the basis of the results of conventional CT, CT cerebral perfusion imaging and TCD.Results In the 20 patients with TIA, conventional CT turned out to be normal. However, persisting abnormal perfusion changes corresponding to clinical symptoms were found in 13 cases with the prolonged TFP. The other 7 cases were normal. TFP of the affected side （ 11.6 ± 3.0） s was significantly prolonged （ t =4. 782 ,P 〈0. 01 ） in comparison with the contralateral side （8.8 ± 1.5 ） s. The difference in CBF was not statistically significant （t = 1. 912, P =0. 073） between the affected side [ （223.9 ±19.6） ml ·min^-1 ·L^-1 ] and the contralateral side [ （227.7 ± 19. 8） ml · min^-1· L^-1 ] . TCD revealed severe stenosis or occlusion of the carotid artery in 10 patients, arteriosclerosis in 6 patients, blood speed decrease in 2 patients, vasospasm in 1 patient. Conclusions Conventional CT can exclude intracerebral diseases. Perfusion CT provides valuable hemodynamic information and shows the extent of perfusion disturbances. TCD can demonstrate abnormalities of the involved arteries in patients with TIA. The combination of these three imaging methods can provide more diagnostic information.