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：

BACKGROUND & AIMS: :Palatal tremor (formerly palatal myoclonus) is an extremely rare, but potentially treatable cause, of objective tinnitus. The tinnitus is thought to be secondary to rhythmic involuntary movements of the soft palate. Its aetiology is variable and it remains difficult to treat. Many different medical and surgical remedies have been tried but none have demonstrated reproducible success. Botulinum toxin has been used in sporadic cases and seems to produce good results. Ten patients with palatal tremor have presented to this department over the last three years. After discussion with the patients with regard to the management of this condition and possible complications, five opted for botulinum toxin therapy and five declined further intervention. Clinical diagnosis was made on the confirmation of soft palate movements synchronous with an audible clicking noise. Five patients underwent botulinum toxin injection into the insertion of the levator and tensor veli palatini muscles. Of the five that were treated with toxin, four showed complete resolution of symptoms after a course of treatment. Only one patient reported transient side effects. This would suggest that botulinum toxin is a safe and effective first line treatment for palatal tremor.

背景与目标： : 腭部震颤 (以前称为腭肌阵挛) 是客观耳鸣的一种极其罕见但可能可治疗的原因。耳鸣被认为是继发于软腭的节律性非自愿运动的继发。它的病因是可变的，仍然很难治疗。已经尝试了许多不同的医学和外科治疗方法，但没有一种方法可以重现成功。肉毒杆菌毒素已用于零星病例，似乎产生良好的效果。在过去三年中，有10名pa震颤患者出现在该部门。在与患者讨论了这种情况的治疗方法和可能的并发症之后，五个人选择了肉毒杆菌毒素治疗，五个人拒绝了进一步的干预。临床诊断是在确认软pa运动与可听见的喀哒声同步进行的。五名患者接受了肉毒杆菌毒素注射到提肌和张肌肌的插入中。在接受毒素治疗的五人中，有四人在一个疗程后症状完全消失。只有一名患者报告了短暂的副作用。这表明肉毒杆菌毒素是治疗pa震颤的安全有效的一线治疗方法。

BACKGROUND & AIMS: :This study links the reduction in jaw physiological tremor around 8 Hz following periodontal mechanoreceptor (PMR) anaesthetisation to changes in coherence between masseteric motor unit discharges. We have recorded single motor unit activity from two separate sites in the right masseter muscle during a low level tonic contraction, both prior to and during anaesthetisation of the peri-incisal PMRs. Anaesthetisation of PMRs decreased coherent activity between motor units circa 8 Hz, and decreased synchrony between the same motor unit pairs. It is proposed that tremor-generating inputs that cause rhythmic synchronisation of masseteric motor units arise from, or are amplified by the PMRs.

背景与目标： : 这项研究将牙周机械感受器 (PMR) 麻醉后8Hz左右的颌骨生理性震颤的减少与咬肌运动单元放电之间的相干性变化联系起来。我们已经记录了在麻醉切牙PMRs之前和期间的低水平强直收缩期间右咬肌中两个独立部位的单个运动单位活动。PMRs的麻醉降低了约8Hz的运动单元之间的相干活性，并降低了相同运动单元对之间的同步性。建议引起咬肌运动单元有节奏同步的震颤产生输入来自pms或被pms放大。

BACKGROUND & AIMS: :Tremor can dominate Parkinson's disease and yet responds less well to dopaminergic medications than do other cardinal symptoms of this condition. Deep brain stimulation can provide striking tremor relief, but the introduction of stimulating electrodes deep in the substance of the brain carries significant risks, including those of hemorrhage. Here, we pioneer an alternative approach in which we noninvasively apply transcranial alternating current stimulation (TACS) over the motor cortex to induce phase cancellation of the rest tremor rhythm. We first identify the timing of cortical oscillations responsible for rest tremor in the periphery by delivering tremor-frequency stimulation over motor cortex but do not couple this stimulation to the on-going tremor-instead, the rhythms simply "drift" in and out of phase alignment with one another. Slow alternating periods of phase cancellation and reinforcement result, informing on the phase alignments that induce the greatest change in tremor amplitude. Next, we deliver stimulation at these specified phase alignments to demonstrate controlled suppression of the on-going tremor. With this technique we can achieve almost 50% average reduction in resting tremor amplitude and in so doing form the basis of a closed-loop tremor-suppression therapy that could be extended to other oscillopathies.

背景与目标： : 震颤可以主导帕金森氏病，但对多巴胺能药物的反应不如这种情况的其他主要症状。深部脑刺激可以缓解震颤，但是在大脑深处引入刺激电极会带来重大风险，包括出血。在这里，我们开创了一种替代方法，在该方法中，我们将经颅交流电刺激 (TACS) 无创地应用于运动皮层，以诱导静止震颤节律的相位消除。我们首先通过在运动皮层上传递震颤频率刺激来确定负责外围静息震颤的皮层振荡的时间，但不要将这种刺激与持续的震颤耦合-相反，节奏只是简单地 “漂移” 彼此相位对齐。相位抵消和强化结果的缓慢交替周期，告知引起震颤幅度最大变化的相位比对。接下来，我们以这些指定的相位比对提供刺激，以证明对持续震颤的受控抑制。通过这种技术，我们可以实现静息震颤幅度的几乎50% 平均降低，从而形成闭环震颤抑制疗法的基础，该疗法可以扩展到其他振荡性疾病。

BACKGROUND & AIMS: BACKGROUND:We investigated the origin of a recently reported ocular microtremor in patients with Parkinson's disease (PD). METHODS:Eye movements were recorded in 2 unselected patients with PD. Two recording techniques were used to control for artifacts: infrared video-oculography and infrared scleral reflection techniques. Head movements were also recorded with 2 different accelerometers. RESULTS:We recorded ocular oscillations in both patients (microtremor). Ocular tremor was accompanied by a recordable (but clinically nonvisible) head tremor of equal fundamental frequency and high coherence with both the eye oscillation and a recordable limb tremor. The eye movements were in the opposite direction to the head oscillation (ie, compensatory) and were suppressed by head restraint. There was no subjective oscillopsia, nor ocular tremor on fundoscopy. CONCLUSIONS:The "ocular tremor" observed in patients with PD disease is a compensatory eye movement secondary to transmitted head tremor, in agreement with clinical wisdom that these patients do not report oscillopsia.

背景与目标：

BACKGROUND & AIMS: :An autopsy case of hereditary peroneal muscular atrophy (PMA) with rigidity and static tremor is presented. The patient developed slowly progressive distal muscular atrophy of the legs at the age of 15 years. By the age of 52 years, PMA became marked associated with pes cavus, and tremor and rigidity of the extremities were noted. Motor and sensory conduction velocities gradually depressed and lost near the end of his life. At autopsy, the major neuropathological abnormalities involved the peripheral nervous systems, and were characterized by axonal atrophy and loss of myelinated fibers. These changes involved both the proximal and distal nerves, being more severely affected in the distal. The pathological changes in other regions of the nervous systems were mainly confined to the spinal cord, dorsal ganglia and spinal nerve roots, and pigmented neurons in the brain stem. Morphometrically, the total fascicular area was much smaller than in control, but the total number of myelinated fibers greatly outnumbered that of control 75,200 to 48,200 at the proximal sciatic nerve and then gradually decreased towards the periphery; however, even in the distal sural nerve, the total number of myelinated fibers exceeded that of control (6820 to 5469). Thus, the density of myelinated fibers were much higher, being 1.5 to 2 times greater, than in control. Its abrupt decline at the distal nerve might account for neurogenic atrophy of the distal musculature. Unmyelinated fibers were slightly increased in density and not atrophic. This case is unique in its clinicopathology and does not belong to any subtypes of PMA including "neuronal plus".

背景与目标： : 提出了遗传性腓骨肌萎缩症 (PMA) 的尸检病例，伴有僵硬和静态震颤。患者在15岁时发展为缓慢进行性远端腿部肌萎缩。到52岁时，PMA与pes cavus明显相关，并注意到四肢震颤和僵硬。运动和感觉传导速度在他生命的尽头逐渐降低并失去。尸检时，主要的神经病理异常涉及周围神经系统，其特征是轴突萎缩和髓鞘纤维丢失。这些变化涉及近端和远端神经，在远端受到更严重的影响。神经系统其他区域的病理变化主要局限于脊髓，背神经节和脊神经根以及脑干中的色素神经元。形态计量学上，总束面积远小于对照组，但有髓纤维的总数大大超过对照组，75,200在坐骨神经近端48,200，然后逐渐向周围减少; 然而，即使在腓肠远端神经，有髓纤维的总数超过对照 (6820至5469)。因此，有髓纤维的密度比对照高得多，是1.5到2倍。它在远端神经的突然下降可能是远端肌肉组织神经源性萎缩的原因。无髓纤维的密度略有增加，没有萎缩。该病例在临床病理上是独特的，不属于PMA的任何亚型，包括 “神经元 +”。

BACKGROUND & AIMS: INTRODUCTION:Despite Essential Tremor (ET) being the commonest movement disorder, there are few studies on the quality of life (QOL) in patients with ET, with most studies employing generic questionnaires. METHODS:We studied QOL in 50 patients with ET attending the outpatient of a hospital using the Quality of life in Essential Tremor (QUEST) questionnaire a disease specific QOL instrument. The severity of tremor was assessed using a modified Fahn Tolosa Marin tremor rating scale (mFTMRS), co morbid anxiety and depression were studied using the Hamilton Anxiety (HARS) and Depression (HDRS) rating scales respectively. We also analyzed the influence of gender, age at presentation, age of onset, duration of tremor, distribution of tremor, family history and use of medications on the QOL. RESULTS:The mean age of onset of tremor was 32.2 ± 18.9 years, mean duration of tremor was 8.4 ± 10.0 years, mean QUEST summary index (QSI) was 24.2 ± 19.2; mean scores in each of the domains were as follows--physical 29.3 ± 26.7, psychosocial 36.4 ± 28.7, communication 23.9 ± 36.9, work & finance 23.5 ± 29.9, hobbies 6.8 ± 17.3. The QSI had significant positive correlation with the mFTMRS, HARS and HDRS. Gender, age at presentation, age of onset, duration of tremor, distribution of tremor, family history and use of medication did not influence the QOL. CONCLUSION:Psychosocial aspects are important in determining the QOL in patients with ET. Tremor severity, co morbid anxiety and depression are associated with a lower QOL whereas tremor characteristics like age of onset, duration, distribution do not influence the QOL.

背景与目标：

BACKGROUND & AIMS: :Essential tremor (ET) is one of the most common movement disorders. However the pathogenesis is as yet unknown, although a genetic cause has long been recognised. Clinical and molecular evidences suggested that the ET gene might contain a CAG expanded region. In a cohort of Italian ET patients Repeat Expansion Detection (RED) approach did not demonstrate large CAG expansions. We extended the study towards specific targets: the channel proteins hSKCa3 and CACNL1A4. Direct assessment of CAG stretches within these two genes did not demonstrate any CAG expansion in affected subjects. Also a case-control analysis failed to reveal any evidence of association, thus excluding these genes as a cause of ET.

背景与目标： : 原发性震颤 (ET) 是最常见的运动障碍之一。然而，尽管早已认识到遗传原因，但其发病机理尚不清楚。临床和分子证据表明，ET基因可能包含CAG扩展区域。在意大利ET患者队列中，重复扩展检测 (RED) 方法未显示CAG大扩展。我们将研究扩展到特定的靶标: 通道蛋白hSKCa3和CACNL1A4。直接评估这两个基因内的CAG延伸并未证明受影响受试者中有任何CAG扩展。病例对照分析也未能揭示任何关联的证据，因此排除了这些基因作为ET的原因。