BACKGROUND & AIMS: INTRODUCTION:Deep Brain Stimulation (DBS) of thalamus in essential tremor (ET) is effective for the treatment of contralateral tremors. Bilateral DBS controls tremors on both sides but is associated with increased morbidity and risks. We evaluated if unilateral surgery had ipsilateral benefits on tremors and thus could be a potentially safer alternative to bilateral DBS. METHODS:Medication refractory ET patients undergoing unilateral thalamic DBS were included and longitudinally followed. Tremor rating scale was used to record total motor, arm tremor and activities of daily living (ADL) scores at baseline, six months and at last visit (three or more years after surgery). Postoperative scores were recorded with DBS turned OFF and ON. RESULTS:Twenty-two patients with a mean follow-up 3.4 ± 0.14 years were enrolled. When baseline scores were compared to scores with the DBS turned ON, significant improvements were noted in total tremor (40%), ADL (67%) and arm tremor scores both on the ipsilateral and the contralateral side at six months and at the last visit of follow-up (all p < 0.05). Ipsilateral arm tremor (∼56%) improvements were milder compared to the contralateral side (∼73%) tremors. CONCLUSION:Unilateral thalamic DBS in ET demonstrates significant long-term benefits for ipsilateral arm tremors and can be offered to higher risk and to select patients.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Essential tremor (ET) is typically measured in the clinic with subjective tremor rating scales which require the presence of a clinician for scoring and are not appropriate for measuring severity throughout the day. Motion sensors can accurately rate tremor severity during a set of predefined tasks in a laboratory. METHODS:We evaluated the ability of motion sensors to quantify tremor during unconstrained activities at home. 20 ET subjects wore a wireless sensor continuously for up to 10 h daily on two days and completed hourly standardized tremor assessments involving pre-defined tasks. Mathematical models were used to predict tremor rating scores from the sensor data. RESULTS:At home tremor scores from hourly standardized assessments correlated with at home tremor scores estimated during unconstrained activities immediately following the standardized assessments. The hourly standardized assessments did not significantly fluctuate throughout the day, while fluctuations in the continuous assessments tended to follow changes in voluntary activity level. Both types of tremor ratings (standardized and continuous) showed high day-to-day test-retest reliability with intraclass correlation coefficients ranging from 0.67 to 0.90 for continuous ratings and 0.77 to 0.95 for standardized ratings. CONCLUSIONS:Results demonstrate the feasibility of continuous monitoring of tremor severity at home, which should provide clinicians with a measure of the temporal pattern of tremor in the context of daily life and serve as a useful tool for the evaluation of novel anti-tremor medications in clinical trials.

背景与目标：

BACKGROUND & AIMS: :Tremor is one of the most disabling symptoms in patients with many movement disorders including Parkinson's disease (PD) and essential tremor (ET). Neural tremor manifests itself as a quasi-periodic fluctuation of the firing rate. We describe a frequency tracking method based on the extended Kalman smoother (EKS) to estimate the instantaneous tremor frequency (ITF) exhibited in binary spike trains detected from neural recordings. Simulation results demonstrate that the EKS frequency tracker can estimate the ITF accurately, even though the signal of interest is not sinusoidal and the noise is not Gaussian. The EKS frequency tracker can obtain a normalized mean squared error (NMSE) as low as 0.1 and performs much better than the conventional approach based on the Hilbert transform.

背景与目标： : 震颤是许多运动障碍患者最致残的症状之一，包括帕金森氏病 (PD) 和原发性震颤 (ET)。神经震颤表现为发射速率的准周期波动。我们描述了一种基于扩展卡尔曼平滑器 (EKS) 的频率跟踪方法，用于估计从神经记录中检测到的二进制尖峰序列中显示的瞬时震颤频率 (ITF)。仿真结果表明，即使感兴趣信号不是正弦信号，噪声也不是高斯信号，EKS频率跟踪器也可以准确估计ITF。EKS频率跟踪器可以获得低至0.1的归一化均方误差 (NMSE)，并且比基于希尔伯特变换的常规方法性能好得多。

BACKGROUND & AIMS: :Movement disorders of various types may occur in relation to viral infections of the central nervous system. They manifest themselves as obvious signs at clinical onset or during the acute phase of an encephalitis (myoclonus, tremor, or parkinsonism), or appear as later sequelae decades after the illness. We describe here a man who developed an unusual movement disorder after a probable viral encephalitis in his childhood. This consisted of a tremor (3-4Hz frequency and 100-150ms duration) of the neck, left shoulder and arm, which persisted unchanged during the ensuing years. The patient regarded this abnormal movement as annoying, but otherwise it did not impair his lifestyle. He subsequently developed the clinical picture of parkinsonism many decades after the onset of tremor, and we speculate that both tremor and parkinsonism can be considered sequelae of encephalitis, but each with a different time-course. The left-sided jerky tremor was an immediate sequela in the childhood; whereas, the rigid-akinetic parkinsonian picture represented a later sequela of the infection in old age. The injured site responsible for both the segmental tremor and the parkinsonism presumably involved the brainstem.

背景与目标： : 各种类型的运动障碍可能与中枢神经系统的病毒感染有关。它们在临床发作时或脑炎急性期 (肌阵挛，震颤或帕金森氏症) 表现为明显的体征，或在疾病后数十年出现后遗症。我们在这里描述了一个在童年时期可能发生病毒性脑炎后出现异常运动障碍的人。这包括颈部，左肩和手臂的震颤 (3-4hz频率和100-150ms持续时间)，在随后的几年中一直保持不变。患者认为这种异常运动令人讨厌，但并没有损害他的生活方式。随后，他在震颤发作数十年后发展了帕金森氏症的临床表现，我们推测震颤和帕金森氏症都可以被认为是脑炎的后遗症，但每个都有不同的时程。左侧的生涩震颤是童年时期的直接后遗症; 然而，僵硬的运动性帕金森病的照片代表了老年感染的后遗症。引起节段性震颤和帕金森病的受伤部位可能涉及脑干。

BACKGROUND & AIMS: :To determine the prevalence of essential tremor (ET) and Parkinson's disease (PD) in a retirement community, all residents of Carefree, Arizona, aged over 65 years were contacted. All participants completed validated questionnaires for PD and ET, and were examined using the Unified Parkinson's Disease Rating Scale. Of 356 individuals evaluated, 155 (43.5%) had tremor; 73 (20.5%) had ET; 26 (7.3%) had PD; and 56 (15.7%) had postural tremor (PT). Thus, a large percentage of individuals were found to have tremor, in the plurality of whom it could be classified as ET. The number of individuals with Parkinson's disease exceeded our expectations.

背景与目标： : 为了确定退休社区中原发性震颤 (ET) 和帕金森氏病 (PD) 的患病率，我们联系了亚利桑那州Carefree的所有65岁以上的居民。所有参与者都完成了PD和ET的验证问卷，并使用统一的帕金森氏病评分量表进行了检查。在356个被评估的个体中，155 (43.5%) 有震颤; 73 (20.5%) 有ET; 26 (7.3%) 有PD; 56 (15.7%) 有姿势性震颤 (PT)。因此，发现很大一部分人患有震颤，其中许多人可以将其归类为ET。帕金森氏病患者的数量超出了我们的预期。

BACKGROUND & AIMS: :Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has proved to be effective for tremor in Parkinson's disease (PD). Most of the recent studies used only clinical data to analyse tremor reduction. The objective of our study was to quantify tremor reduction by STN DBS and antiparkinsonian medication in elderly PD patients using an objective measuring system. Amplitude and frequency of resting tremor and re-emergent resting tremor during postural tasks were analysed using an ultrasound-based measuring system and surface electromyography. In a prospective study design nine patients with advanced PD were examined preoperatively off and on medication, and twice postoperatively during four treatment conditions: off treatment, on STN DBS, on medication, and on STN DBS plus medication. While both STN DBS and medication reduced tremor amplitude, STN DBS alone and the combination of medication and STN DBS were significantly superior to pre- and postoperative medication. STN DBS but not medication increased tremor frequency, and off treatment tremor frequency was significantly reduced postoperatively compared to baseline. These findings demonstrate that STN DBS is highly effective in elderly patients with advanced PD and moderate preoperative tremor reduction by medication. Thus, with regard to the advanced impact on the other parkinsonian symptoms, STN DBS can replace thalamic stimulation in this cohort of patients. Nevertheless, medication was still effective postoperatively and may act synergistically. The significantly superior efficacy of STN DBS on tremor amplitude and its impact on tremor frequency in contrast to medication might be explained by the influence of STN DBS on additional neural circuits independent from dopaminergic neurotransmission.

背景与目标： : 丘脑底核 (STN) 的深部脑刺激 (DBS) 已被证明对帕金森氏病 (PD) 的震颤有效。最近的大多数研究仅使用临床数据来分析震颤的减轻。我们研究的目的是使用客观测量系统量化STN DBS和抗帕金森病药物对老年PD患者的震颤减轻。使用基于超声的测量系统和表面肌电图分析了姿势任务期间静息震颤和再次出现静息震颤的幅度和频率。在一项前瞻性研究设计中，对9例晚期PD患者进行了术前和服药检查，并在四种治疗条件下进行了两次术后检查: 停药，STN DBS，药物治疗和STN DBS加药物治疗。尽管STN DBS和药物治疗均降低了震颤幅度，但单独使用STN DBS以及药物和STN DBS的组合显着优于术前和术后药物治疗。与基线相比，STN DBS而不是药物会增加震颤频率，并且术后震颤频率显着降低。这些发现表明，STN DBS在老年晚期PD和通过药物减少中度术前震颤的患者中非常有效。因此，关于对其他帕金森症状的晚期影响，STN DBS可以代替该患者队列中的丘脑刺激。尽管如此，药物在术后仍然有效，并且可能具有协同作用。与药物相比，STN DBS对震颤幅度的显着优势及其对震颤频率的影响可能是STN DBS对独立于多巴胺能神经传递的其他神经回路的影响。

BACKGROUND & AIMS: :Recent advances in our understanding of the clinical and molecular features of the fragile-X mental-retardation 1 gene, FMR1, highlight the importance of single-gene disorders. 15 years after its discovery, FMR1 continues to reveal new and unexpected clinical presentations and molecular mechanisms. Loss of function of FMR1 is a model for neurodevelopmental and behavioural disorders, including mental retardation, autism, anxiety, and mood instability. In addition, overexpression and CNS toxicity of FMR1 mRNA causes a late-onset neurodegenerative disorder, the fragile-X-associated tremor/ataxia syndrome (FXTAS). A similar mechanism is probably involved in premature ovarian failure, which affects up to 20% of female carriers of an altered FMR1 gene.

背景与目标： : 我们对脆性X智力低下1基因FMR1的临床和分子特征的理解的最新进展突显了单基因疾病的重要性。在发现FMR1 15年后，它继续揭示新的和意想不到的临床表现和分子机制。FMR1功能丧失是神经发育和行为障碍的模型，包括智力低下，自闭症，焦虑和情绪不稳定。此外，FMR1 mRNA的过表达和CNS毒性会导致迟发性神经退行性疾病，即脆性X相关的震颤/共济失调综合征 (FXTAS)。类似的机制可能与卵巢早衰有关，其影响多达20% 的FMR1基因改变的女性携带者。

BACKGROUND & AIMS: BACKGROUND:Physiological tremor is an intrinsic and highly variable motor output that is sensitive to alteration in both neuromuscular function and/or changing task demands. Given that any tremor increase can severely influence fine motor performance, there is a requirement to clarify what factors lead to increased tremor. Identification of those factors that alter tremor may be particularly pertinent for elderly persons, who often exhibit a decline in postural control and amplified tremor. The aim of this study was to examine the effect of whole body posture (seated vs standing) on multiple segment tremor and forearm electromyogram (EMG) activity of younger and older individuals. METHODS:Fourteen older and 12 young participants performed a bilateral pointing task. Tremor data were collected using accelerometers attached to the forearm, hand, and finger segments of each arm. Surface EMG data were also collected from the extensor digitorum muscle of each arm. RESULTS:Although the pattern of tremor was similar between age groups, older participants exhibited increased hand and finger tremor amplitude and increased EMG activity across all postural conditions. For older individuals, tremor increases were greatest when the participant performed the task in a standing position. All age-related increases in hand and/or finger tremor were confined to increases in peak power between 8 Hz and 12 Hz. CONCLUSIONS:From a clinical perspective, these findings illustrate that using multiple segment tremor analyses can provide additional insight into potential age-related tremor differences. Additionally, the fact that postural position had a pronounced effect on tremor in older individuals suggests that body posture should be considered as a potential confounding factor when assessing tremor differences between population groups.

背景与目标：

BACKGROUND & AIMS: :Essential Tremor is the most common form of movement disorder. Aggregation in families suggests a strong genetic component to disease. Linkage and association studies have identified several risk loci but the specific causal variants are still unknown. A recent study using whole exome sequencing identified a rare nonsense variant in the FUS gene (p.Q290X) that segregated with Essential Tremor in a large French Canadian family. In addition, two other rare FUS variants were identified (p.R216C and p.P431L) in Essential Tremor patients however co-segregation analysis with disease was not possible. In the present study, we sequenced all 15 exons of FUS in 152 familial probands with Essential Tremor and genotyped three reported FUS variants in 112 sporadic Essential Tremor patients and 716 control subjects recruited at Mayo Clinic Florida. Only known synonymous SNPs unlikely to be pathogenic were detected in our sequencing and not any of the recently identified mutations or novel ones. We conclude that the FUS mutations associated with risk of Essential Tremor are probably a rare occurrence.

背景与目标： : 原发性震颤是最常见的运动障碍形式。家庭中的聚集表明疾病具有很强的遗传成分。连锁和关联研究已经确定了几个风险位点，但具体的因果变异仍然未知。最近的一项使用全外显子组测序的研究确定了FUS基因 (p.Q290X) 中的一种罕见的无意义变体，该变体与法国加拿大大家庭的原发性震颤分离。此外，在原发性震颤患者中鉴定出了另外两个罕见的FUS变体 (p.R216C和p.P431L)，但是无法与疾病进行共分离分析。在本研究中，我们对152例患有原发性震颤的家族性先证者中的FUS的所有15个外显子进行了测序，并对佛罗里达州梅奥诊所招募的112例散发性原发性震颤患者和716名对照受试者进行了基因分型。在我们的测序中仅检测到已知的不太可能具有致病性的同义snp，而没有检测到任何最近发现的突变或新突变。我们得出的结论是，与原发性震颤风险相关的FUS突变可能很少见。

BACKGROUND & AIMS: :Muscle tremors mimicking atrial or ventricular arrhythmias are unusual. If present, however, misdiagnosis and consequently inappropriate treatments are possible. The authors present a patient with Parkinson's disease who was referred for evaluation of the need for oral anticoagulation because of persistent atrial flutter.

背景与目标： : 模仿心房或室性心律失常的肌肉震颤是不寻常的。然而，如果存在，误诊和因此不适当的治疗是可能的。作者介绍了一名帕金森氏病患者，该患者因持续性心房扑动而被转诊以评估口服抗凝的必要性。

BACKGROUND & AIMS: :We screened 662 subjects comprising 462 essential tremor (ET) subjects (285 sporadic, 125 with family history, and 52 probands from well-characterized ET pedigrees) and 200 controls and identified pathogenic NOTCH2NLC GGC repeat expansions in 4 sporadic ET patients. Two patients were followed up for >1 decade; one with 90 repeats remained an ET phenotype that did not evolve after 40 years, whereas another patient with 107 repeats developed motor symptoms and cognitive impairment after 8 to 10 years. Neuroimaging in this patient revealed severe leukoencephalopathy; diffusion-weighted imaging hyperintensity in the corticomedullary junction and skin biopsy revealed intranuclear inclusions suggestive of intranuclear inclusion body disease (NIID). No GGC repeats of >60 units were detected in familial ET cases and controls, although 4 ET patients carried 47 to 53 "intermediate" repeats. NOTCH2NLC GGC repeat expansions can be associated with sporadic ET. Carriers presenting with a pure ET phenotype may or may not convert to NIID up to 4 decades after initial tremor onset. ANN NEUROL 2020;88:614-618.

背景与目标： : 我们筛选了662名受试者，包括462名原发性震颤 (ET) 受试者 (285名散发性，有家族史的125名，以及来自特征明确的ET家系的52名先证者) 和200名对照，并在4名散发性ET患者中鉴定了致病性NOTCH2NLC GGC重复扩张。对两名患者进行了> 1个十年的随访; 一个有90次重复的患者仍然是ET表型，在40年之后没有发展，而另一个有107次重复的患者在8至10年之后出现了运动症状和认知障碍。该患者的神经影像学显示严重的白质脑病; 皮质带交界处的弥散加权成像高强度和皮肤活检显示核内夹杂物提示核内包涵体疾病 (NIID)。尽管有4名ET患者携带47至53个 “中间” 重复，但在家族性ET病例和对照组中未检测到> 60  单位的GGC重复。NOTCH2NLC GGC重复扩展可能与零星ET有关。具有纯ET表型的携带者在最初震颤发作后长达4年可能会或可能不会转化为NIID。神经2020;88:614-618。

BACKGROUND & AIMS: BACKGROUND:Task-specific tremor in musicians severely impairs fine motor control. However, little is known about its pathophysiology. Here, we quantify electromyography (EMG) properties in primary bowing tremor-in particular, muscular coactivation-to determine whether primary bowing tremor affects a specific frequency range of coactivation. METHODS:We quantitatively compared EMG properties of the wrist muscles between 4 professional violinists who had task-specific tremor and 4 age-matched healthy controls. RESULTS:We observed bowing tremor-specific muscular coactivation in the frequency range of 3 to 8 Hz only in the patients but not in the healthy controls. No muscular activity was observed at the resonance-frequency range. CONCLUSIONS:Our findings indicate an association between coactivation and bowing tremor at a specific frequency range (3-8 Hz). The absence of EMG activity and coactivation in the mechanical-reflex frequency of the wrist suggests that central mechanisms play a more dominant role than mechanical-reflex mechanisms in primary bowing tremor.

背景与目标：

BACKGROUND & AIMS: Importance:Essential vocal tremor (EVT) is a neurologic voice disorder characterized by periodic fluctuations in pitch and loudness that can hinder intelligibility. Defining the normative range of vocal tremor frequency may assist in diagnosis and provide insight into disease mechanisms. Objective:To characterize the normative voice tremor frequency in EVT (in hertz). Design, Setting, and Participants:Cross-sectional observational study of 160 patients with EVT. The setting was a tertiary voice center. Participants were identified from a database of consecutive patients diagnosed as having laryngeal movement disorders between January 1, 1990, and April 1, 2017. Main Outcomes and Measures:The following 3 methods measured the frequency of tremor experienced by patients with EVT: perceptual method, computerized peak detection method, and laryngeal electromyography method. Within-person and population-level tremor frequencies were compared across modalities to assess measurement reliability and consistency and to characterize the normal distribution of tremor frequencies in this population. Results:Among 160 participants (median age, 70 years; interquartile range [IQR], 64-77 years; 90.6% female [n = 145]), the median frequency of EVT was consistently between 4 and 5 Hz across all 3 methods (perceptual, 4.8 Hz [IQR, 4.4-5.5 Hz]; computerized peak detection, 4.6 Hz [IQR, 4.2-5.0 Hz]; and laryngeal electromyography, 4.3 Hz [IQR, 3.8-5.0 Hz]). The mean in-person differences between each measurement method were not clinically meaningful (range, 0.1-0.5 Hz). Including all interquartile ranges across measurement modalities, the normative tremor frequency range for EVT was 3.8 to 5.5 Hz. Conclusions and Relevance:To our knowledge, this is the largest study to date to characterize the normal frequency of tremor in patients with EVT. The normative frequency of EVT (range, 3.8-5.5 Hz) falls within a much narrower range than previously reported. Those whose frequency is outside this range may still have EVT but should be carefully evaluated for potential other causes of vocal tremor. Defining characteristics of EVT may aid appropriate diagnosis and improve understanding of this disease.

背景与目标：

BACKGROUND & AIMS: OBJECTIVE:Tremor is the most common movement disorder which is most often either essential or caused by Parkinson's disease. The differentiation of these disorders at the initial stage may be difficult. Objective assessment of the efficacy of tremor medications is only possible by instrumental measurements. The aim of this study was to determine whether the computer assisted tremor analysis system CATSYS 2000 can help in the differentiation of parkinsonian from essential tremor. METHODS:The rhythmicity and maximal frequency of fast alternating hand and finger movements, simple reaction time and postural instability were recorded in healthy controls (n = 18), patients with Parkinson's disease (n = 39) and essential tremor (n = 37). Data were digitally converted and statistically analyzed. RESULTS:Tremor intensity, median frequency and frequency distribution showed characteristic differences in the three groups. Performance in fast alternating movements of hands and fingers were significantly worse in both tremor groups compared to the healthy controls. CONCLUSIONS:The data also indicated that quantitative measurements of tremor parameters must be performed on both sides, because the presence of significant side differences support the diagnosis of Parkinson's disease. The method presented can be used to objectively analyze tremor and performance in rhythmic movements. The results show that it helps to differentiate parkinsonian from essential tremor as well as to predict disease course and the effectiveness of therapy. Multivariate statistical analysis of tremor and movement performance also provides an opportunity to study the pathogenesis of human tremor.

背景与目标：

BACKGROUND & AIMS: INTRODUCTION:Embarrassment is commonly reported in essential tremor (ET) patients yet there is no formal tool to assess embarrassment in ET. Our aim was to develop such a tool and to assess its clinimetric properties. A quantitative measure of embarrassment could be used to assess response to treatment in clinical practice and clinical trials. METHODS:Based on surveys of international tremor experts and ET patients, we constructed the Essential Tremor Embarrassment Assessment (ETEA), a brief, easily administered, 14-item self-assessment scale. The ETEA was assessed for validity, reliability and other clinimetric properties in 75 ET patients. RESULTS:Forty-seven tremor experts from eight countries were surveyed. On average, they estimated that 75% of their patients experienced embarrassment, yet there was very little agreement (range = 10-95%). Among ET patients, three-quarters (77.3%) reported at least occasional embarrassment due to their tremor and one-third (36.4%) reported daily embarrassment. ETEA scores correlated with a tremor disability questionnaire score (p = 0.02 and p = 0.01) and Center for Epidemiologic Studies Depression Scale scores (p<0.001 and p<0.001). Test-retest reliability was high (p<0.001). Factor analysis identified four factors, explaining 62.4% of the variance. For the major factors (I and II), high internal consistency was found (Cronbach's alpha = 0.85 and 0.74). CONCLUSION:Embarrassment is commonly experienced by ET patients. The ETEA is a reliable and valid tool to measure embarrassment in patients with this disease.

背景与目标：