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.

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.

Toward understanding the role of genomic repeat elements in neurodegenerative diseases

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

Tremor大鼠皮质内ERK信号通路相关蛋白表达的变化

目的研究ERK!信号通路相关蛋白在癫痫状态下的改变,以探讨ERK信号转导通路在癫痫发病机制中的作用。方法实验分为两组,分别为Tremor大鼠组和Wistar大鼠组。通过Western Blot方法检测两组大脑皮质内ERK蛋白和p-ERK蛋白含量的异常变化。结果通过PCR鉴定了Tremor大鼠,试验分为Tremor组(实验组)和Wistar组(对照组)。利用western Blot方法测定ERK1/2和p-ERK1/2蛋白在Tremor大鼠和Wistar大鼠的皮质中均有表达,Tremor大鼠的ERK1/2和p-ERK的蛋白含量分别为0.140 3和0.734 4,Wistar组大鼠的ERK1/2和p-ERK的蛋白含量分别为0.170 9和0.975 4。结论 ERK1/2和p-ERK蛋白在癫痫大鼠皮质内的表达显著减少,说明ERK信号通路在癫痫状态下被抑制。

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.

Wireless accelerometer configuration for monitoring Parkinson’s disease hand tremor

Parkinson’s disease is neurodegenerative in nature and associated with characteristic movement disorders, such as hand tremor. Wireless accelerometer applications may advance the quality of care for Parkinson’s disease patients. The acceleration waveform of the respective hand tremor can be recorded and stored for post-processing and progressive status tracking. A wireless accelerometer configuration for monitoring Parkinson’s disease hand tremor is presented. The proposed configuration is envisioned to be conducted with the assistance of a caregiver. For initial engineering proof of concept simulated Parkinson’s disease tremor is recorded through a wireless accelerometer node and contrasted to a statically positioned and tandem activated wireless accelerometer node. Statistical significance is acquired regarding the quantification of the simulated Parkinson’s disease tremor acceleration waveform and statically positioned acceleration waveform, while demonstrating a considerable degree of accuracy, consistency, and reliability.

Anomalous tremor before 2008 Ms8.0 Wenchuan earthquake: a review

In this paper we give a review of several previously published papers on anomalous tremors observed before the 2008 Ms8.0 Weuchuan earthquake. Based on the observed time and frequency shifts between coastal and inland stations, we discussed some methods to distinguish different kinds of microseisms, and speculated that a pre-earthquake typhoon might have caused a ＂mainland-originated microseism＂ which in turn trig- gered the earthquake.

Novel frameshift mutation in the SACS gene causing spastic ataxia of charlevoix-saguenay in a consanguineous family from the Arabian Peninsula:A case report and review of literature

BACKGROUND Familial cases of autosomal recessive spastic ataxia of charlevoix-saguenay have not been reported in the Arabian Peninsula,although the consanguineous marriage rate is very high.We report the first family from the Arabian Peninsula harboring a novel frameshift mutation in the SACS gene.CASE SUMMARY A 33-year-old man presented to our neurology clinic with balance problems and weakness of distal upper and lower limbs.He was previously clinically diagnosed with Friedreich's ataxia.However,the severity of polyneuropathy and the electrodiagnostic studies(EDX)findings are atypical features of Friedreich’s ataxia,and the deterioration was attributed to diabetic neuropathy.Close examination of other family members identified cerebellar ataxia,lower-limb pyramidal signs,peripheral neuropathy,and magnetic resonance imaging findings characterized by pontine linear hypointensities.Genetic testing for Friedreich’s ataxia did not yield a diagnosis.Whole exome sequencing identified a novel frameshift germline mutation in the SACS gene termed c.5824_5827delTACT using the transcript NM_014363.5,which is predicted to cause premature termination of the sacsin protein at amino acid position 1942(p.Tyr1942Metfs*9)and disrupts the sacsin SRR3 and domains downstream from it.The mutation segregated with the disease in the family.CONCLUSION Our data add to the spectrum of mutations in the SACS gene and argues for a need to implement suitably integrated clinical and diagnostic services,including next generation sequencing technology,to better classify ataxia in this area of the world.

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.

Clinical and genetic study of ataxia with vitamin E deficiency: A case report

BACKGROUND Ataxia with vitamin E deficiency(AVED)is a type of autosomal recessive cerebellar ataxia.Clinical manifestations include progressive cerebellar ataxia and movement disorders.TTPA gene mutations cause the disease.CASE SUMMARY We report the case of a 32-year-old woman who presented with progressive cerebellar ataxia,dysarthria,dystonic tremors and a remarkably decreased serum vitamin E concentration.Brain magnetic resonance images showed that her brainstem and cerebellum were within normal limits.Acquired causes of ataxia were excluded.Whole exome sequencing subsequently identified a novel homozygous variant(c.473T>C,p.F158S)of the TPPA gene.Bioinformatic analysis predicted that F185S is harmful to protein function.After supplementing the patient with vitamin E 400 mg three times per day for 2 years,her symptoms remained stable.CONCLUSION We identified an AVED patient caused by novel mutation in TTPA gene.Our findings widen the known TTPA gene mutation spectrum.

Transition of Thalassaemia and Friedreich ataxia from fatal to chronic diseases

Thalassaemia major(TM) and Friedreich's ataxia(FA) are autosomal recessive inherited diseases related to the proteins haemoglobin and frataxin respectively. In both diseases abnormalities in iron metabolism is the main cause of iron toxicity leading to increased morbidity and mortality. Major efforts are directed towards the prevention of these diseases and also in their treatment using iron chelation therapy. Both TM and FA are endemic in Cyprus, where the frequency per total population of asymptomatic heterozygote carriers and patients is the highest worldwide. Cyprus has been a pioneering nation in preventing and nearly eliminating the birth of TM and FA patients by introducing an organized health structure, including prenatal and antenatal diagnosis. Effective iron chelation therapy, improved diagnostic methods and transfusion techniques as well as supportive therapy from other clinical specializations have improved the survival and quality of life of TM patients.Despite the tiresome clinical management regimes many TM patients are successful in their professional lives, have families with children and some are now living well into their fifties. The introduction of deferiprone led to the elimination of cardiac failure induced by iron overload toxicity, which was the major cause of mortality in TM. Effective combinations of deferiprone with deferoxamine in TM patients caused the fall of body iron to normal physiological ranges. In FA different mechanisms of iron metabolism and toxicity apply to that of TM, which can be targeted with specific iron chelation protocols. Preliminary findings from the introduction of deferiprone in FA patients have increased the hopes for improved and effective therapy in this untreatable condition. New and personalised treatments are proposed in TM and FA. Overall, advances in treatments and in particular of chelation therapy using deferiprone are transforming TM and FA from fatal to chronic conditions. The paradigm of Cyprus in the prevention and treatment of TM can be used for application worldwide.

Prenatal diagnosis of spinocerebellar ataxia type 3/Machado-Joseph disease in China's Mainland A case report

Spinocerebellar ataxia type 3/Machado-Joseph disease （SCA3/MJD） is a progressive, currently untreatable and ultimately fatal ataxic disorder that belongs to the group of neurological disorders known as CAG-repeat or polyglutamine diseases. Here, we present the first prenatal diagnosis of SCA3/MJD in China's Mainland in a woman who was known to carry an expanded CAG-trinucleotide repeat in the MJD1 gene. After evaluating motivation and psychological tolerance of the couple, amniocentesis was performed after 14 weeks of gestation. Polymerase chain reactions followed by T-vector cloning and direct sequencing were employed to evaluate the CAG-repeat number of the fetal MJD1 gene. We identified a truncated CAG expansion of 78 repeats in the MJD1 gene of the fetus compared with 81 repeats in his mother.

Statistics of Seismic Tremors with Harmonic Overtones Recorded at Syowa Station, Antarctica: October 2014-March 2015

During the period from October 2014 to March 2015, a total number of 82 seismic tremors and 66 ice-quakes were identified in both three-component short-period seismographs (HES) and broadband seismographs (STS-1) at Syowa Station (SYO), Antarctica. Statistics of the number of these tremors indicated that many tremors were likely to occur when large increases in temperature and/or wind speed during the period. This implied that the rapid increase in temperature enhanced a melting speed of cryosphere environment with generating seismic energy;the tremors were also excited by stormy conditions, associated with interactive resonance between sea-ices and oceanic swells. The characteristic tremors of harmonic overtones with strong amplitudes were explained by repetitive sources, suggesting inter-glacial asperities such as the collision of icebergs and fast sea-ice, calving of glaciers/ice-streams at the coastal environment of Antarctica. These high amplitude tremors occurred independently from other majority types of events, characterized by non-linear, small amplitude and weak signals at the stormy condition and rapid increase in temperature.

Gas-dynamic phenomena caused by rock mass tremors and rock bursts

Similar to coal, rock and gas ejections, rock mass tremors and rock bursts are among the most serious natural hazards accompanying the underground extraction of coal. Gas-dynamic phenomena caused by rock mass tremors and rock bursts observed as transient states of air parameters in mining headings,are usually generated as a result of a change in the geometry of headings and the release of considerable amounts of gases. Particular significance is attributed to transient states caused by disasters, which are often accompanied by rapid incidents, presenting threats to the life and health of the underground crew.In Polish mining there are known examples of transient states of air parameters recorded during gasdynamic phenomena, e.g. tremors and rock bursts. The paper presents the case studies of rapid seismic incidents to show how records in mine monitoring systems broaden the knowledge about the transient states of air parameters in mining headings generated because of them.

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.