Magnetic resonance-guided focused ultrasound for essential tremor:a prospective,single center,single-arm study

The safety and effectiveness of magnetic resonance-guided focused ultrasound thalamotomy has been broadly established and validated for the treatment of essential tremor.In 2018,the first magnetic resonance-guided focused ultrasound system in Chinese mainland was installed at the First Medical Center of the PLA General Hospital.This prospective,single center,open-label,single-arm study was part of a worldwide prospective multicenter clinical trial(ClinicalTrials.gov Identifier:NCT03253991)conducted to confirm the safety and efficacy of magnetic resonance-guided focused ultrasound for treating essential tremor in the local population.From 2019 to 2020,10 patients with medication refractory essential tremor were recruited into this open-label,single arm study.The treatment efficacy was determined using the Clinical Rating Scale for Tremor.Safety was evaluated according to the incidence and severity of adverse events.All of the subjects underwent a unilateral thalamotomy targeting the ventral intermediate nucleus.At the baseline assessment,the estimated marginal mean of the Clinical Rating Scale for Tremor total score was 58.3±3.6,and this improved after treatment to 23.1±6.4 at a 12-month follow-up assessment.A total of 50 adverse events were recorded,and 2 were defined as serious.The most common intraoperative adverse events were nausea and headache.The most frequent postoperative adverse events were paresthesia and equilibrium disorder.Most of the adverse events were mild and usually disappeared within a few days.Our findings suggest that magnetic resonance-guided focused ultrasound for the treatment of essential tremor is effective,with a good safety profile,for patients in Chinese mainland.

Neural computational modeling reveals a major role of corticospinal gating of central oscillations in the generation of essential tremor

Essential tremor, also referred to as familial tremor, is an autosomal dominant genetic disease and the most common movement disorder. It typically involves a postural and motor tremor of the hands, head or other part of the body. Essential tremor is driven by a central oscillation signal in the brain. However, the corticospinal mechanisms involved in the generation of essential tremor are unclear. Therefore, in this study, we used a neural computational model that includes both monosynaptic and multisynaptic corticospinal pathways interacting with a propriospinal neuronal network. A virtual arm model is driven by the central oscillation signal to simulate tremor activity behavior. Cortical descending commands are classified as alpha or gamma through monosynaptic or multisynaptic corticospinal pathways, which converge respectively on alpha or gamma motoneurons in the spinal cord. Several scenarios are evaluated based on the central oscillation signal passing down to the spinal motoneurons via each descending pathway. The simulated behaviors are compared with clinical essential tremor characteristics to identify the corticospinal pathways responsible for transmitting the central oscillation signal. A propriospinal neuron with strong cortical inhibition performs a gating function in the generation of essential tremor. Our results indicate that the propriospinal neuronal network is essential for relaying the central oscillation signal and the production of essential tremor.

Understanding Tremor in Rapid Upper Limb Movements Using 3D Accelerometers Data

Tremor is a manifestation of a variety of human neurodegenerative diseases, notably Parkinson’s disease (PD) and Essential Tremor (ET), both affecting millions worldwide. PD is primarily caused by a progressive loss of dopamine neurons in the nigrostriatal system that leads to widespread motor symptoms such as bradykinesia, rigidity, tremor and postural instability. ET typically involves a tremor of the arms, hands or fingers. No definitive test or biomarker is yet available for PD or ET, so the rate of misdiagnosis is relatively high. As tremor is a very common feature at the onset of both diseases, it is crucial to be able to characterize it. This is made possible using acce?lerometers to quantify the tremor amplitude and frequency. In this work we aim to find tasks involving upper limb movements that are suitable to modulate both types of tremor. Four tasks were tested, differing on whether the arms moved together or alternatingly and whether loads were added. Significant differences in tremor measures were found when patients were asked to perform simultaneous rapid arms movements with loads placed on their wrists. These results may allow the design of an efficient fMRI protocol for identifying the cortical circuits responsible for the modulation of tremor.

Visual function alterations in essential tremor: A case report

Our purpose is to report alterations in contrast sensitivity function(CSF)and in the magno,parvo and koniocellular visual pathways by means of a multichannel perimeter in case of an essential tremor(ET).A complete evaluation of the visual function was performed in a 69-year old patient,including the analysis of the chromatic discrimination by the Fansworth–Munsell 100 hue test,the measurement of the CSF by the CSV-1000E test,and the detection of potential alteration patterns in the magno,parvo and koniocellular visual pathways by means of a multichannel perimeter.Visual acuity and intraocular pressure(IOP)were within the ranges of normality in both eyes.No abnormalities were detected in the fundoscopic examination and in the optical coherence tomography(OCT)exam.The results of the color vision examination were also within the ranges of normality.A signi¯cant decrease in the achromatic CSFs for right eye(RE)and left eye(LE)was detected for all spatial frequencies.The statistical global values provided by the multichannel perimeter confirms that there were significant absolute sensitivity losses compared to the normal pattern in RE.In the LE,only a statistically significant decrease in sensitivity was detected for the blue-yellow(BY)channel.The pattern standard deviation(PSD)values obtained in our patient indicated that there were significant localized losses compared to the normality pattern in the achromatic channel of the RE and in the red-green(RG)channel of the LE.Some color vision alterations may be present in ET that cannot be detected with conventional color vision tests,such as the FM 100 Hue.

Essential tremor:A three-dimensional neurosphere in vitro model to assess the neurotoxicity of harmane

Objectives: To use a novel in vitro model of three-dimensional(3D) neurosphere cultures to assess neurotoxic or neuroprotective effects with harmane as a model compound.Methods: A reproducible model of 3D spheroids was developed from embryonic mouse cortical neurons,using molded agarose micro-wells;this method seems particularly practical as it is customizable and widely available and does not require specific cell treatments or assay components different from 2D cultures, allowing for the easy transposition of routine protocols. To assess the neurotoxic effects of harmane, a resazurin assay was performed to measure cell viability, and a highly sensitive fluorometric method, based on the oxidation of dichlorodihydrofluorescein, was applied to measure eventually induced reactive oxygen species(ROS) after exposure to harmane at increasing concentrations of 50 100,and 250 μm.Results: Hydrogel microwells facilitated the assembly of spheroids containing neurons and glial cells into a complex 3D structure and prevented the agglomeration of spheroids. Exposure to harmane induced cytotoxicity in 3D neural spheroids, which was correlated with harmane concentrations, with a 27%reduction in viability at 250 μm. Harmane that did not induce significant levels of oxidative stress was detected for all tested concentrations.Conclusion: This 3D neurosphere model mimics a neuronal microenvironment, allowing a fine study of neurodegenerative disorders and the effects of chemicals on the brain. This model opens novel opportunities, not only from a pathogenetic point of view but also from a therapeutic perspective.

Mechanism of Inhibitory Effect of Essential Oil from Valerianae Jatamansi Rhizoma et Radix on Activation of Microglia

[Objectives]To investigate the inhibitory effect and possible mechanism of essential oil from Valerianae Jatamansi Rhizoma et Radix on microglia activation induced by lipopolysaccharide(LPS).[Methods]The LPS-induced microglia activation model was established and treated with different doses of essential oil from Valerianae Jatamansi Rhizoma et Radix.MTT assay was used to detect cell viability,ELISA to detect IL-6 secretion,RT-PCR to detect mRNA expression levels of IL-6,IL-1β,NF-κB,and IκBα,Western blotting to detect the protein expression of IL-6,IL-1β,NF-κB,IκBα,and their phosphorylated products.[Results]Compared with the normal control group,the model group showed increased IL-6 content(P<0.01),upregulated mRNA and protein levels of IL-6,IL-1β,and NF-κB(P<0.01),and elevated ratio of P-IκBα/IκBα(P<0.05).Compared with the model group,4 and 2μg/L essential oil from Valerianae Jatamansi Rhizoma et Radix reduced the content of IL-6(P<0.05),while 4,2,and 1μg/L essential oil from Valerianae Jatamansi Rhizoma et Radix down-regulated the mRNA and protein levels of IL-6,IL-1β,and NF-κB to varying degrees(P<0.05 or P<0.01),up-regulate the mRNA expression of IκBα(P<0.05 or P<0.01),and decreased the ratio of P-IκBα/IκBα(P<0.05 or P<0.01).[Conclusions]Essential oil from Valerianae Jatamansi Rhizoma et Radix can inhibit LPS-induced microglia activation,and its mechanism may be related to the inhibition of the NF-κB/IκBαsignaling pathway.

加味天麻钩藤饮对阴虚阳亢型高血压患者血浆ET、PRA、AⅡ的影响

目的 探讨加味天麻钩藤饮降压效果及对血浆内皮素 (ET)、肾素活性 (PRA)、血管紧张素 (AⅡ )的影响。方法 146例阴虚阳亢型高血压病患者随机分为两组 ,10 2例给予加味天麻钩藤饮 ,44例给予巯甲丙脯酸、硝苯地平。治疗前后测定血浆ET、PRA、AⅡ水平。结果 (1)治疗组降压总有效率 88 2 4% ,与对照组相当 ,对主要症状改善率优于对照组 ;(2 )治疗后治疗组血浆ET、AⅡ水平低于对照组 ,但均高于正常人。结论 加味天麻钩藤饮既能降低ET、AⅡ含量 ,又能明显降低血压。

老年原发性高血压患者血压控制与血浆BNP、ET-1含量的关系

目的 探讨老年原发性高血压患者经药物治疗后血脑利钠肽 (BNP)、内皮素 - 1(ET- 1)含量与血压控制情况的关系。方法 测定 5 6例经药物治疗后老年原发性高血压患者的血浆 BNP、ET- 1含量。结果 血压控制正常组血浆 BNP和 ET- 1含量均显著低于血压控制不理想组 (分别为 P<0 .0 5和 P<0 .0 1)。结论 血浆BNP、ET- l的含量能反映老年原发性高血压患者的血压控制情况 。

老年男性高血压患者血浆ADM和ET-1含量变化的意义

目的:探讨老年男性高血压患者血浆肾上腺髓质素(ADM)、内皮素-1(ET-1)含量变化的临床意义。方法:用放射免疫分析测定62例老年男性高血压患者血浆ADM、ET-1含量,并与35例年龄、性别匹配的健康老年人对照。结果:高血压组血浆ADM、ET-1含量显著高于正常对照组(P<0.01),两者均随高血压分级1、2、3级组逐渐递增(P<0.01,<0.05);血压控制不良者明显高于血压控制良好者(P<0.01),病情重组显著高于病情轻组(P<0.01);伴肾功能受损者也显著高于肾功能正常者(P<0.01);血浆ET-1含量平均增幅明显高于血浆ADM(P<0.01);高血压组血浆ADM与ET-1含量呈正相关(r=0.394,P<0.01);正常对照组两者含量不相关(r=0.172,P>0.05)。结论:老年男性高血压患者血浆舒血管活性肽ADM含量显著增高,可能是机体的一种代偿性自身调节机制,以此抑制ET-1等缩血管活性肽增高对血压调节产生不良的影响,对机体起到自身代偿性保护作用。

阻塞性睡眠呼吸暂停低通气综合征患者血浆ET-1、NO水平的变化及nCPAP对其影响

目的 观察阻塞性睡眠呼吸暂停低通气综合征 (OSAHS)患者经鼻持续气道内正压通气 (nCPAP)治疗前后血浆ET 1、NO水平的变化 ,并探讨其临床意义。方法 选择OSAHS无EH者 (A组 ) ,OSAHS合并EH者 (B组 ) ,正常对照 (C组 ) ,三组行PSG监测。用放免法测血浆ET 1 ,NO采用硝酸还原酶法。A、B两组施以nCPAP治疗。用袖带加压法观察血压。结果 ①与C组相比 ,A组AHI、ET 1 /NO增高 ,最低SaO2 下降 ,治疗后情况相反 ;A组治疗前后ET 1 /NO分别与AHI、最低SaO2 均明显相关 (r分别为 0 40 8、- 0 569)。②与C组相比 ,B组MBP、AHI、ET 1 /NO增高 ,最低SaO2 下降 ,治疗后情况相反 ;B组治疗前后MBP分别与ET 1 /NO、AHI、最低SaO2 均明显相关 ,r分别为 0 439、0 51 5、- 0 455。结论 ①OSAHS可引起血压升高 ,某些血管舒缩因子比例失衡可能在OSAHS合并EH中起一定的病理作用 ;

原发性高血压病伴房颤患者血浆ET和BNP的含量变化

目的 :探讨原发性高血压伴房颤患者血浆ET、BNP的含量变化。方法 :应用IRMA法测定 4 8例原发性高血压病伴房颤患者和 82例原发性高血压病无房颤患者血浆ET、BNP含量 ,并以 5 6例健康人作对照。结果 :原发性高血压病伴房颤组血浆ET、BNP含量均非常显著高于正常人组 (p <0 0 0 1)。结论 :深入研究原发性高血压病患者血浆ET、BNP的含量变化 ,对预防和治疗原发性高血压心脏病将有重要的临床意义。

原发性高血压患者治疗前后血浆ET和E选择素检测的临床意义

目的:探讨了原发性高血压患者治疗前后血浆ET和E选择素水平及临床意义。方法:应用放免法检测了39例原发性高血压患者治疗前后血浆ET水平,酶联免疫法检测E选择素水平,并与35名正常健康人作比较。结果:原发性高血压患者治疗前后血浆ET和E选择素水平非常显著地高于正常人组水平(P<0.01),经治疗3个月后则与正常人组比较无显著性差异(P>0.05)。结论:血浆ET和E选择素的异常升高是原发性高血压发病的病理因素之一,对诊断、治疗和预后均有重要的临床价值。

原发性高血压病患者治疗前后血浆ET、BNP、ANF检测的临床意义

目的:探讨了原发性高血压病患者治疗前后血浆ET、BNP和ANF水平的变化及意义。方法:应用放射免疫分析对53例原发性高血压病患者进行了治疗前后血浆ET、BNP和ANF测定,并与35名正常健康人作比较。结果:原发性高血压病患者在治疗前血浆ET、BNP和ANF水平均非常显著地高于正常人组(P<0.01),经治疗一个月后与正常人组比较仍有显著性差异(P<0.05)。结论:检测原发性高血压病患者血浆ET、BNP和ANF水平的变化对疗效观察、预后判断均具有重要的临床价值。

ET-1基因突变位点的组合分析与原发性高血压病的关系

目的:了解内皮素-1(ET-1)基因138A/-、K198N、G8002A3个突变位点多态性组合与海南汉族原发性高血压(EH)的关系。方法:应用等位基因特异性PCR技术,对201例海南汉族EH患者及311例海南汉族正常对照组ET-1基因多态性位点进行检测,利用统计学方法分析3个位点多态性组合与EH的关系。结果:138A/-、K198N、G8002A多态位点分别可检测出4A/4A、4A/3A、3A/3A3种基因型,GG、GT、TT 3种基因型和GG、GA、AA 3种基因型。多态位点组合分析发现有两组基因型4A3AGG-GG、3A3A-GG-GG在病例组中出现的频率远大于对照组;两组基因型4A4A-GT-GG、4A3A-GTGG在对照组中出现的频率大于病例组,差异均具有统计学意义(P<0.05)。结论:4A3A-GG-GG和3A3A-GG-GG这两组基因型串联可能会增加高血压的发病几率,4A4A-GT-GG和4A3A-GT-GG这两组基因型串联可能会降低高血压的发病几率。

ET和PV患者的临床特征及血栓和出血并发症分析

目的:探讨原发性血小板增多症(ET)和真性红细胞增多症(PV)患者的临床特征、血栓和出血并发症的发生规律。方法:收集合2016年世界卫生组织(WHO)诊断标准的133例ET和45例PV患者的病例资料,分析ET、PV及ET+PV患者的动静脉血栓、出血事件的发生率,检测血栓和出血事件的患者JAK2、CALR及MPL驱动基因突变情况,分析血管事件与基因突变发生率和年龄之间的相关性,分析患者驱动基因、血栓和出血事件的类型、频率及年龄分布的特点。结果:ET、PV及ET+PV患者的血栓事件发生率高于各自的出血事件发生率,ET、PV及ET+PV患者的动脉血栓事件发生率高于各自的静脉血栓事件发生率,差异均有统计学意义(P<0.01);动脉血栓事件中脑血栓事件(16.29%)最常见,有血栓事件的ET患者中,年龄和JAK2V617F基因突变率大于无事件ET患者,差异有统计学意义(P<0.05);JAK2V617F和CALR驱动基因突变双阳性的ET患者,可合并有血栓事件。结论:ET和PV患者血栓事件较出血事件更常见,其中脑血栓事件最常见;有血栓事件的ET患者的年龄更大,JAK2V617F基因突变率更高,JAK2V617F和CALR突变双阳性的ET患者可合并有血栓事件。

4D printing of soft orthoses for tremor suppression

Tremor is an involuntary and oscillatory movement disorder that makes daily activities difficult for affected patients. Hand tremor-suppression orthoses are noninvasive, wearable devices designed to mitigate tremors. Various studies have shown that these devices are effective, economical, and safe;however, they have drawbacks such as large weight, awkward shape, and rigid parts. This study investigates different types of tremor-suppression orthoses and discusses their efficiency, mechanism,benefits, and disadvantages. First, various orthoses(with passive, semi-active, and active mechanisms) are described in detail.Next, we look at how additive manufacturing(AM) has progressed recently in making sensors and actuators for application in tremor orthoses. Then, the materials used in AM are further analyzed. It is found that traditional manufacturing problems can be solved with the help of AM techniques, like making orthoses that are affordable, lighter, and more customizable. Another concept being discussed is using smart materials and AM methods, such as four-dimensional(4D) printing, to make orthoses that are more comfortable and efficient.

DRD3基因Ser9Gly多态性与特发性震颤相关性的meta分析

目的系统评价DRD3基因Ser9Gly多态性与特发性震颤的相关性。方法计算机检索pubmed、Web of Science、中国知网(Chinese National Knowledge Infrastructure,CNKI)、维普数据库、中国生物医学文献数据库、万方数据库,收集2019年10月前有关DRD3基因Ser9Gly多态性与特发性震颤的病例-对照研究。应用统计学软件Stata14.0进行Meta分析。结果共纳入8项病例-对照研究,病例组1456例,对照组1651例。Meta分析结果显示,显性模型中GG+GA基因型的群体发病风险高于AA基因型的群体[OR=1.16,95%CI(1.00,1.35),P=0.043]。基于人种的亚组分析显示,DRD3基因Ser9Gly多态性与特发性震颤之间的相关性仅存在于高加索人群中。结论高加索人群中DRD3基因Ser9Gly多态性与特发性震颤具有相关性,且GG+GA基因型的存在增加发病风险。

原发性高血压患者治疗前后血浆ET-1和血清NO、CGRP检测的临床意义

目的:探讨原发性高血压患者治疗前后血浆ET-1和血清NO、CGRP水平的变化及临床意义。方法:应用放射免疫分析和化学法对33例原发性高血压患者进行了治疗前后血浆ET-1和血清NO、CGRP测定,并与35名正常健康人作比较。结果:原发性高血压患者在治疗前血浆ET-1水平非常显著地高于正常人组(P<0.01),而血清NO、CGRP水平又非常显著地低于正常人组(P<0.01),经治疗2个月后则与正常人组比较无显著性差异(P>0.05)。血浆ET-1水平与NO、CGRP水平呈显著负相关(r=-0.5728、-0.4822,P<0.01)。结论:检测原发性高血压患者血浆ET-1和血清NO、CGRP水平的变化对探讨其发病机制提供了有价值的实验室依据。

中医外治疗法治疗特发性震颤疗效的Meta分析

目的:针对中医外治疗法治疗特发性震颤的临床疗效进行系统评估,为临床应用提供依据。方法:检索中国知网等数据库,获得中医外治疗法治疗特发性震颤的随机对照试验。对符合收录标准的研究做质量评价,并做Meta分析。结果:收录了12篇随机对照试验研究以供研究,涉及652名患者。总有效率Meta分析、合并效应量结论、震颤评分、汉密尔顿抑郁量表(Hamilton Depression Rating Scale,HAMD)评分等显著降低。结论:中医外治疗法治疗特发性震颤在疗效、震颤评分、HAMD评分、不良反应方面优于西药,但此结论依然期待更多高质量、大样本文献进行后续验证。

益精稳压方早期干预对SHR血压、ET-1及TM水平的影响

目的:观察早期应用中药益精稳压方干预对大鼠高血压发生的预防抑制作用以及可能的作用机制。方法:取自发性高血压大鼠(SHR)32只,随机分为模型组、中药干预低、中、高剂量组,各8只,WKY大鼠8只为正常对照组。中药干预高、中、低剂量组分别予益精稳压中药3.16、1.58、0.79g/mL灌胃,正常组与模型组予等量蒸馏水灌胃。观察各组治疗前、中、后血压、ET-1及TM水平。结果:与正常组比较,模型组及中药干预组大鼠血压、血ET-1及血TM水平明显上升,差异有统计学意义(P<0.01);与模型组比较,中药中、高剂量组血压、血ET-1及血TM水平下降,差异有统计学意义(P<0.05)。同组大鼠治疗前后比较,中药中、高剂量组大鼠血压升高进展延缓,ET-1及血TM水平升高幅度下降。结论:益精稳压方早期干预可延缓自发性高血压大鼠高血压进展,其机制可能与降低ET-1及TM水平有关。