Assistive techniques and their added value for tremor classification in multiple sclerosis

Tremor occurs in about half of multiple sclerosis(MS)patients.MS tremor has a broad frequency range of 2.5-7 Hz,with a higher prevalence of postural tremor(44%)compared to intentional tremor(6%)(Alusi et al.,2001).Tremor may affect the upper and lower extremities,head,and trunk,and may even affect the vocal cords in isolated cases of palatal tremor.MS tremor is classically attributed to lesions of the brain stem,cerebellum,or cerebellar peduncles,and tremor intensity has been shown to correlate with the number of lesions or their functional connections.However,recent work has demonstrated that inflammatory damage to the cerebello-thalamic and cortico-thalamic pathways might also play an important role in causing tremor,as it co-occurs with other signs and symptoms of MS such as dysarthria,dysmetria,dysdiadochokinesia,and dystonia(Alusi et al.,2001).

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.

Quantifying Kinematic Tremor in an NGLY1-Deficient Individual: A Case Study

NGLY1 Deficiency is an autosomal recessive congenital disorder that has been identified in less than 100 individuals. Most individuals with NGLY1 Deficiency display hyperkinetic movement disorders, including choreiform, athetoid, dystonic myoclonic, dyskinetic, and dysmetric movements. Developing a consistent and concise consensus on the classification and evaluation of tremors is essential to forward the research and treatment of tremors. It has also been reported that some individuals with NGLY1 Deficiency demonstrate tremor, but such tremor has never been formally investigated. The primary objective of this study is to determine if an individual with NGLY1 Deficiency demonstrates an identifiable tremor during a series of arm movements and, if so, describe the frequency and power characteristics of that tremor. Arm movement kinematics were obtained using a 16-camera Vicon system, and time series trajectory waveforms for three planes of a marker placed on the hand were developed. Custom MATLAB scripts were utilized to compute Fast Fourier Transformations of the data within the identified waveform segments. A mean frequency of 2.30 Hz (SD = 1.05) with a mean power of 5.02 |P1(f)| (SD = 4.63) suggests that our participant’s kinematic data did display a persistent tremor in both hands across all tasks and movement planes. Analyses of the reaching hand and the non-reaching hand suggest the participant displayed an action tremor in both postural and intention (kinetic) tremors. Future directions should include assessing additional individuals with NGLY1 Deficiency to determine if the tremor is a distinguishable disorder behavior. Additionally, evaluating other anatomical sites, such as the elbow, head, and lower limbs, would provide further insights into the characteristics of this tremor.

Hypergonadotrophic Hypogonadism with Cerebellar Ataxia in a Twenty-Six-Year-Old Female: A Case Report

Gordon Holmes Syndrome is a rare inherited disease characterized by both neurological and reproductive signs and symptoms. Most patients develop neurologic challenges in early adulthood and cerebellar ataxia occurs as the disease progresses. In the majority of patients, hypogonadism is hypogonadotropic but rarely hypergonadotropic. We report a case of a 26-year-old female in Nigeria, with hypergonadotropic hypogonadism and cerebellar atrophy from a non-consanguineous marriage and no family history.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Cell-based therapeutic strategies for treatment of spinocerebellar ataxias:an update

Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein aggregation.Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy impairment.Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system.Spinocerebellar ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait deficits.Over the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is available.Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration.So far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and 3.However,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration used.Nonetheless,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural network.Meanwhile,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still unknown.To establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease.Further studies are needed to determine the best route of administration,without neglecting the possible risks of repetitive transplantation that these approaches so far appear to demand.Despite the challenges ahead of us,cell-transplantation therapies are reported to have transient but beneficial outcomes in spinocerebellar ataxias,which encourages efforts towards their improvement in the future.

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.

Ataxia-telangiectasia mutated plays an important role in cerebellar integrity and functionality

Accumulating evidence indicates that ataxia-telangiectasia mutated kinase is critical for maintaining cellular homeostasis and that it has both nuclear and cytoplasmic functions.However,the functions of ataxia-telangiectasia mutated that when lost lead to cerebellar degeneration are still unknown.In this review,we first describe the role of ataxia-telangiectasia mutated in cerebellar pathology.In addition to its canonical nuclear functions in DNA damage response circuits,ataxia-telangiectasia mutated functions in various cytoplasmic and mitochondrial processes that are critically important for cellular homeostasis.We discuss these functions with a focus on the role of ataxia-telangiectasia mutated in maintaining the homeostatic redox state.Finally,we describe the unique functions of ataxia-telangiectasia mutated in various types of neuronal and glial cells including cerebellar granule neurons,astrocytes,and microglial cells.

Compound heterozygous mutations in tripeptidyl peptidase 1 cause rare autosomal recessive spinocerebellar ataxia type 7:A case report

BACKGROUND Spinocerebellar ataxia recessive type 7(SCAR7)is a rare clinical manifestation beginning in childhood or adolescence.SCAR7 is caused by tripeptidyl peptidase 1(TPP1)gene mutations,and presents with cerebellar ataxia,pyramidal signs,neurocognitive impairment,deep paresthesia,and cerebellar atrophy.CASE SUMMARY Here,we describe a 25-year-old female patient in China who presented with increasing difficulty walking,falling easily,shaking limbs,instability holding items,slurred speech,coughing when drinking,palpitations,and frequent hunger and overeating.Magnetic resonance imaging showed cerebellar atrophy.Whole exome sequencing detected two compound heterozygous mutations in the TPP1 gene:c.1468G>A p.Glu490Lys and c.1417G>A p.Gly473Arg.Considering the patient’s clinical presentation and genetic test results,we hypothesized that complex heterozygous mutations cause TPP1 enzyme deficiency,which may lead to SCAR7.CONCLUSION We report the first case of SCAR7 from China.We also identify novel compound heterozygous mutations in the TPP1 gene associated with SCAR7,expanding the range of known disease-causing mutations for SCAR7.

PRF1突变致家族性嗜血细胞综合征二例

目的探讨PRF1基因突变致家族性嗜血细胞淋巴组织细胞增多症2型(FLH2型)临床症状和基因型特点。方法报道2例河北省儿童医院神经内科住院一家系患儿的临床资料,提取患儿及其父母基因组DNA,采取靶向外显子捕获测序技术检测致病突变,并对检测到的突变进行Sanger测序验证。结果该家系2例患儿均以共济失调为首发症状,病情反复,查脑脊液白细胞数升高,头颅MRI提示多发脱髓鞘改变。基因检测显示为PRF1基因突变c.1189-1190dupTG(p.H398Afs*23)和c.394G>A(p.G132R)的复合杂合子,前者来自于父亲,后者来自于母亲。妹妹给予干细胞移植治疗,目前病情缓解。结论PRF1基因突变致FLH2型符合基因杂合变异遗传学特点。儿童可以中枢神经系统受累为首发症状,表现为共济失调、周围性面神经瘫痪,基因可早期诊断,干细胞移植治疗是获得长期生存的方法之一。

基于大数据分析的大扭矩机器人悬臂关节震颤控制技术

大扭矩机器人悬臂产生的信号量较大,运用大数据分析技术能够对海量信号进行精准分析,以期解决悬臂关节震颤控制成功率较低的问题。为此,构建大扭矩机器人悬臂关节运动学模型,获取悬臂关节运动学分析结果;使用自适应滤波器获取机器人工作信号,应用数据挖掘技术获取机器人悬臂关节震颤特征;最后,使用线性傅里叶拟合方法优化机器人悬臂关节震颤控制算法,以实现机器人悬臂关节震颤控制。构建应用测试环节,测试结果表明:基于大数据分析的震颤控制技术抑制振动成功率较高,可有效地解决悬臂关节震颤问题。

矿震与冲击地压防治研究进展

矿震与冲击地压是采矿领域亟待解决的热点、难点和瓶颈问题,为了有效控制矿震与冲击地压,综述矿震定义与分类、矿压假说及矿震与冲击地压防治技术,回顾切顶卸压理论及其在中厚金矿采空区处理与卸压开采、中厚及以下煤矿沿空留巷中的应用,并比较其与110工法的差异。据此,给出矿震定义,指出矿震与冲击地压发生的条件类似,针对厚矿体开采提出深埋坚硬顶板控制爆破切槽放顶技术。研究表明:控制爆破切槽放顶技术仍然是未来矿震与冲击地压防治中释放并转移高地压的主要方法,它还可将深埋厚矿体的“砌体梁”简化成弹簧岩梁承载体系。

HPLC法测定tremor大鼠脑组织中谷氨酸和GABA含量

目的建立测定tremor大鼠(tm)脑内海马组织中GLU及GABA浓度的高效液相色谱(HPLC)方法。方法冰上剥离13wk的tm/Wistar大鼠海马组织,低温匀浆处理,利用邻苯二甲醛(OPA)柱前衍生HPLC法结合荧光检测器测定GLU和GABA的含量。0.1mol·L-1醋酸钾和甲醇进行二元梯度洗脱,峰面积定量。结果GLU的线性方程为Y^=1E+06X(r2=0.9937),线性范围为0.15～5.88mg·L-1,具有良好的线性关系,在0.74、1.47、3.68mg.L-13个浓度下样本回收率分别为97.7%、98.9%、100.5%;样品中GLU日内变异系数为3.8%,隔日测定后,日间变异系数为5.9%;GABA的线性方程为Y^=4E+06X(r2=0.998),线性范围为0.10～2.15mg·L-1,具有良好的线性关系,在0.2、0.5、1.0mg·L-13个浓度下样本回收率分别为98.3%、101.0%、102.7%;样品GABA日内变异系数为2.3%,隔日测定后,日间变异系数为3.9%。结论该方法较简便、快速且干扰相对较小,满足测定要求,可用于氨基酸的含量测定研究。

Joint observation of long period tremor signals with broadband seismometer,tiltmeter and gravimeter

We report here the observation result of joint observation of long period tremor signals with broadband seismome-ter,tiltmeter and gravimeter at the HUST(Huazhong University of Science and Technology)station.The observed data were compared and analyzed.Since 2005,the several tens of abnormal tremor signals which are weak,com-plex and duration of 2 to 3 days have been synchronously recorded by the different instruments.The tremor signals have the periodic domain in the range of 3 to 5 minutes,20 to 30 minutes and even more than 1 hour.The observa-tion shows such tremors are a physical existence.The analysis indicates that a part of the tremors caused by the typhoon from the western Pacific Ocean.These tremors have a close relationship with wind velocity of typhoon and distance between the typhoon center and the station.Except these,the cause of others is still unclear.

人体手臂静止性震颤的负刚度吸振效果研究

提出采用负刚度吸振器控制人体手臂静止性震颤的方法,以便有效减小传递到前臂的动态响应.首先,建立含负刚度吸振器的人体手臂耦合动力学模型;然后,推导得到各关节位置的幅频响应表达式,并采用序列二次规划算法给出负刚度吸振器的最优设计参数.利用最优设计参数分别计算得到正弦激励和随机激励对应耦合系统的动态响应曲线.为了便于对比,给出未安装负刚度吸振器和安装传统线性吸振器时人体手臂各关节的动态响应.计算结果表明,负刚度吸振器对人体手臂静止性震颤引起各关节的动态响应抑制效果显著优于传统线性吸振器.

揿针配合感觉统合训练治疗共济失调型脑性瘫痪疗效观察

目的观察揿针配合感觉统合训练治疗共济失调型脑性瘫痪的临床疗效。方法将105例共济失调型脑性瘫痪患者随机分为对照A组、对照B组和联合组,每组35例。对照A组采取揿针治疗,对照B组采用感觉统合训练治疗,联合组采用揿针配合感觉统合训练治疗。观察3组治疗前后粗大运动功能测试量表-88(gross motor function measure-88,GMFM-88)各功能区(A~E区)评分、步态各项指标(步长、步速、步宽)、平衡控制能力各项指标(躯干前后标准差、躯干左右标准差及躯干总标准差)、表面肌电信号各项指标[内收肌及腓肠肌积分肌电值(integrated electromyography,IEMG)、表面肌电均方根值(root mean square,RMS)]及儿科生活质量量表(the pediatric quality of life inventory,PedsQL)各项评分(生理功能、情感功能、社交功能)的变化情况,比较3组临床疗效。结果3组治疗前后GMFM-88各功能区评分、步态各项指标、平衡控制能力各项指标、表面肌电信号各项指标及PedsQL各项评分组内比较,差异具有统计学意义(P<0.01)。联合组治疗后GMFM-88各功能区评分及步长、步速均明显高于对照A组和对照B组,步宽及表面肌电信号各项指标均明显低于对照A组和对照B组,差异均具有统计学意义(P<0.05)。联合组及对照B组治疗后平衡控制能力各项指标均明显低于对照A组,PedsQL各项评分均明显高于对照A组,差异均具有统计学意义(P<0.05)。联合组总有效率为94.3%,显著高于对照A组的74.3%和对照B组的68.6%,差异均具有统计学意义(P<0.05)。结论揿针配合感觉统合训练治疗共济失调型脑性瘫痪疗效确切,可增强核心肌群稳定性,改善患者步态,提高粗大运动及平衡能力。

基于Apriori算法与因子分析探讨帕金森病的中医药用药规律

目的:运用复杂网络分析中医药治疗帕金森病用药的相互关系。方法:收集中医药方剂治疗帕金森病的相关文献,建立中药数据库,采用SPSS软件进行复杂网络分析探讨各药物相互关系。结果:中医药治疗帕金森病高频用药排名居前6位为白芍、熟地黄、当归、甘草、钩藤、天麻,并对其进行聚类分析及因子分析,得出7类组方和11类公因子。运用关联规则分析得出中药用药以白芍-熟地黄核心药对进行加减。结论:中医药治疗帕金森病常以滋阴养血为主要原则,平肝息风、化痰散结、开窍醒神等为常用治疗方法,其核心药对为白芍-熟地黄。

从芍药甘草汤方证与药量探讨胞轮振跳的治疗

胞轮振跳是临床中的难治性疾病,该病严重影响患者的情绪及生活质量。目前临床治疗手段有限,西医多以手术为主,且容易反复,创伤性较大。中医药治疗该病不良反应少且疗效稳固。芍药甘草汤主治肝脾阴虚证,而胞轮振跳的病机之一则为肝脾阴虚,这是与芍药甘草汤证的契合点。因此,根据异病同治原则,该方治疗此类疾病是辨病与辨证结合的临床思路的体现。通过文献考证古今度量衡质量的单位换算,芍药(白芍)与炙甘草的用量需达60 g以上方可获得良好临床疗效。本文总结了芍药甘草汤的临床使用经验,并结合文献从方义与药量角度论证其治疗胞轮振跳的可行性与合理性。

儿童急性小脑性共济失调1例报告

回顾性分析1例新型冠状病毒(SARS-CoV-2)感染后急性小脑性共济失调患儿的临床资料和诊治过程,并进行相关文献复习。患儿,女,4岁11个月,因“咳嗽2周,发热3天”入院。入院第2天出现吟诗样语言,独坐不稳,走路不稳。予静脉人免疫球蛋白注射液总量2 g/kg(分4天)及静脉甲基强的松龙2 mg·kg^(-1)·d^(-1)治疗,病情明显好转后予醋酸泼尼松片口服(1 mg·kg^(-1)·d^(-1))并出院。出院11天电话随访患儿已基本恢复正常,遂停醋酸泼尼松治疗。文献报道3例患儿,均为男性,年龄分别为5岁、13岁、15岁;均为SARS-CoV-2感染后1~2周发病;临床表现均有共济失调步态;2例予静脉甲基强的松龙治疗,1例未予特殊治疗,3例均在2月内恢复正常。SARS-CoV-2感染所致急性小脑性共济失调一般为感染后1~2周出现,临床多表现为共济失调步态,多为感染后免疫反应所致,预后良好。

弹性绳带训练联合Frenkel体操对伴共济失调的脑卒中患者平衡及步行功能的影响

目的:观察弹性绳带训练联合Frenkel体操对伴有共济失调的脑卒中患者平衡及步行功能的影响。方法:将40例伴共济失调脑卒中患者随机分成绳带组和对照组各20例。2组患者均进行常规的康复训练和站立平衡步行训练。绳带组采用弹性绳带加压下进行站立位平衡和步行训练方案。治疗前后对2组患者进行Berg平衡量表(BBS)、10m步行测试(10MWT)、3米起立-走测试(TUGT)及共济失调等级评定量表(SARA)的评估。结果:治疗6周后,2组BBS和10MWT评分均较治疗前显著提高(P<0.01),TUGT和SARA评分均较治疗前显著降低(P<0.05);绳带组的BBS评分和10MWT评分明显高于对照组(P<0.01),TUGT和SARA评分明显低于对照组(P<0.05)。结论:弹性绳带训练联合Frenkel体操能显著提高伴共济失调的脑卒中患者的平衡及步行功能。