特发性震颤的临床和电生理学特点

目的 探讨特发性震颤(EI)的临床和电生理学特点.方法 回顾性分析并比较33例ET患者(ET组)和30例生理性震颤患者(对照组)的震颤类型、程度、幅度和负重对其的影响,以总结ET的临床和电生理学特点.结果 ET组患者动作性震颤(KT)的震颤程度明显高于对照组,震颤幅度明显大于对照组(均P＜0.01);而姿势性震颤(PT...     

Validation of digital spiral analysis as outcome parameter for clinical trials in essential tremor

Essential tremor, one of the most prevalent movement disorders, is characterized by kinetic and postural tremor affecting activities of daily living. Spiral drawing is commonly used to visually rate tremor intensity, as part of the routine clinical assessment of tremor and as a tool in clinical trials. We present a strategy to quantify tremor severity from spirals drawn on a digitizing tablet. We validate our method against a well‐established visual spiral rating method and compare both methods on their capacity to capture a therapeutic effect, as defined by the change in clinical essential tremor rating scale after an ethanol challenge. Fifty‐four Archimedes spirals were drawn using a digitizing tablet by nine ethanol‐responsive patients with essential tremor before and at five consecutive time points after the administration of ethanol in a standardized treatment intervention. Quantitative spiral tremor severity was estimated from the velocity tremor peak amplitude after numerical derivation and Fourier transformation of pen‐tip positions. In randomly ordered sets, spirals were scored by seven trained raters, using Bain and Findley's 0 to 10 rating scale. Computerized scores correlated with visual ratings (P < 0.0001). The correlation was significant at each time point before and after ethanol (P < 0.005). Quantitative ratings provided better sensitivity than visual rating to capture the effects of an ethanol challenge (P < 0.05). Using a standardized treatment approach, we were able to demonstrate that spirography time‐series analysis is a valid, reliable method to document tremor intensity and a more sensitive measure for small effects than currently available visual spiral rating methods. © 2011 Movement Disorder Society     

Computerized tremor analysis of valproate-induced tremor: a comparative study of controlled-release versus conventional valproate

PURPOSE: Valproate (VPA) induces postural tremor in 6-45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity. METHODS: In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n=10) or CR-VPA (n=8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of >or=8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors. RESULTS: At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p<0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing. CONCLUSIONS: This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak-trough variation with VPA than with CR-VPA.     

Is essential tremor predominantly a kinetic or a postural tremor? A clinical and electrophysiological study

Both postural and kinetic tremors may occur in essential tremor (ET), however the relative contribution of each is not clear. ET has been variably defined with respect to kinetic and postural tremors. To examine the relative severity of postural and kinetic tremors in ET, 50 ET cases from a clinic and 55 from a community underwent a videotaped tremor examination. Kinetic and postural tremors were rated using a validated clinical rating scale (score range, 0-3). Thirty-one cases also underwent accelerometry to precisely quantify tremor amplitude. In clinic cases, the mean postural tremor rating was 1.25 (S.D., 0.89). The mean kinetic tremor rating was 52% higher (1.90; S.D., 0.57; P < 0.001). The community cases had similar characteristics. Sixty percent of the 105 cases had postural tremor ratings scoring 0 or 1 (no tremor or low amplitude, intermittent tremor). In clinic cases, the mean amplitude of postural tremor during tremor analysis was 0.51 mm (S.D., 0.66 mm), and the mean amplitude of kinetic tremor was 2.91 mm (S.D., 2.11 mm; P < 0.01). Similar values were obtained for community cases. These quantitative data suggest that kinetic tremor is more severe than postural tremor in ET. The majority of cases had mild or absent postural tremor. Despite this, ET is defined only as a postural tremor in many studies. Our data argue for a more consistent inclusion of kinetic tremor in diagnostic criteria for ET.     

Characterization of tremor in phenylketonuric patients

Tremor of unknown origin is detected in 10–30% of early–treated and in more than 30% late–treated phenylketonuric patients. With the aim of characterizing tremor in phenylketonuria, we carried out a systematic study in 54 patients aged 6 to 37 years. Tremor examination was done by applying the WHIGET Tremor Rating Scale and by accelerometer recording (BYOPAC System MP100WSW). Age at diet onset, IQ test results, concomitant plasma phenylalanine levels and index of dietary control were also studied. Tremor was not observed at rest in any case, but was apparent in 22 patients (40.7%) when carrying out a kinetic task. In 15 patients tremor was also evident during maintenance of a postural task at a frequency ranging between 7.5 and 12.7 Hz. Frequency of tremor was not significantly modified by loading the arms or by increasing muscle contraction. Patients with tremor had a later age at onset of phenylalanine restricted diet (p < 0.001). Other treatment–related variables did not differ between patients with and without tremor. Our results of the neurophysiological examination suggest that tremor in phenylketonuric patients is dependent on a dysfunction of central nervous system networks and may be an index of cerebral damage.     

Muscle loading as a method to isolate the underlying tremor components in essential tremor and Parkinson's disease

Tremor is clinically evaluated and classified on the basis of its response to limb posture (resting, postural, and kinetic tremor), but the mechanisms underlying this powerful influence remain unclear and no satisfactory method exists to identify or quantify underlying tremor subtypes. Postural change is closely linked to changes in gravitational load. We therefore assessed the effect of changes in muscle load on essential tremor (ET) and parkinsonian tremor (PT) independently of postural change. A motor accurately delivered a series of constant (0.2-1.2 Nm) flexion and extension torques about the affected wrist while subjects maintained a constant wrist angle by isometrically contracting wrist flexors or extensors against the applied loads. Linear regression of tremulous electromyogram (EMG) spectral peak amplitude against the applied loads estimated the magnitudes of the load-dependent (LDT) and load-independent (LIT) tremor components. The amplitude of ET was linearly related to increase in gravitational load. It thus contained a large LDT component and a small or absent LIT component. Muscle loading revealed significant LDT and LIT components in PT. LIT was dominant at zero load (classic rest tremor) but both components were present during loading (classic postural tremor). Muscle loading more clearly identifies tremor subtypes than postural effects alone. The method could be applied in clinical and pathophysiological studies.     

Different effects of essential tremor and Parkinsonian tremor on multiscale dynamics of hand tremor

ObjectiveEssential tremor (ET) and Parkinsonian tremor (PT) are often clinically misdiagnosed due to the overlapping characteristics of their hand tremor. We aim to examine if ET and PT influence the multiscale dynamics of hand tremor, as quantified using complexity, differently, and if such complexity metric is of promise to help identify ET from PT.MethodsForty-eight participants with PT and 48 with ET performed two 30-second tests within each of the following conditions: sitting while resting arms or outstretching arms horizontally. The hand tremor was captured by accelerometers secured to the dorsum of each hand. The complexity was quantified using multiscale entropy.ResultsCompared to PT group, ET group had lower complexity of both hands across conditions (F > 34.2, p < 0.001). Lower complexity was associated with longer disease duration (r² > 0.15, p < 0.009) in both PT and ET, and within PT, greater Unified Parkinson's Disease Rating Scale-III UPDRS-III scores (r² > 0.18, p < 0.009). Receiver-operating-characteristic curves revealed that the complexity metric can distinguish ET from PT (area-under-the-curve > 0.77, cut-off value = 48 (postural), 49 (resting)), which was confirmed in a separate dataset with ET and PT that were clearly diagnosed in prior work.ConclusionsThe PT and ET have different effects on hand tremor complexity, and this metric is promising to help the identification of ET and PT, which still needs to be confirmed in future studies.SignificanceThe characteristics of multiscale dynamics of the hand tremor, as quantified by complexity, provides novel insights into the different pathophysiology between ET and PT.     

微电极导向立体定向手术治疗原发性震颤

目的：探讨丘脑腹外则Vim核中与震颤症状相关的神经细胞电活动的规律,总结丘脑毁损术治疗原性震颤（ET）的临床效果和安全性。方法：对42例ET患者行单侧微电极导向的丘脑毁损术。采用FAHN的临床震颤评分法对其中11例患者术前及术后进行定量评估和分析。结果：Vim核中神经细胞的簇状电活动节律与肢体震颤的节律有肯定的一致性,毁损这些与震颤症状相关的神经细胞后,所有ET患者手术对侧肢体的震颤完全消失;震颤的整体改善率52％,特殊动作和功能改善54％,功能残疾改善率77％,长期随访疗效稳定,其中40例患者的震颤症状密切相关,毁损这些细胞能完全永久性地消除震颤症状。     

Intention tremor of the head in patients with essential tremor.

Patients with essential tremor (ET) have kinetic arm tremor; this tremor can also have an intentional component. We are unaware of reports of intention tremor of the head in ET. Our aims were to describe, provide electrophysiological data and video documentation of, and estimate the prevalence of intention tremor of the head in our sample. Ten (9.0%; 95% confidence interval = 4.7%-14.3%) of 111 patients had intention tremor of the head; in 7 it involved the neck and in 3 the chin. These patients trended toward having more severe kinetic arm tremor and they had more severe intention tremor of the arms. These observations provide further support for the evolving view that the cerebellum may be involved in ET.     

合并静止性震颤的原发性震颤患者临床特点分析

目的了解北京地区社区中老年人原发性震颤(essential tremor,ET)的临床特征及其与预后的关系。方法2000年在北京城区、近郊平原、远郊山区调查了2835名55岁以上中老年人,采用筛查和临床诊断两步法确诊患者。发现ET患者135例,对其中合并静止性震颤的患者进行分析,并于2004年对其进行随访。结果其中合并上肢静止性震颤患者17例,占12.6%,合并静止性震颤组震颤总分、头部震颤的比例、肢体震颤总分均明显高于对照组。两组年龄、性别组成、病史无显著性差异,姿势性震颤和动作性震颤的程度差异不明显。4年后随访到13例(13/17),其中3例死亡,实际调查的10例中有9例仍诊断为ET,另1例诊断为临床很可能ET。结论有相当部分社区ET患者可以合并静止性震颤,合并静止性震颤的患者提示病情较重。     

Quantitative tremor measurement with the computerized analysis of spiral drawing

BACKGROUND AND PURPOSE: There are several instrumental and clinical methods to assess hand tremor. The clinical methods, e.g. rating scales, have the advantage that they are available to most clinicians; however, they require experience, and are not as repeatable as instrumental methods. The study describes the use of a method based on a digitizing tablet and artificial neuronal networks in the assessment of tremor. The Automated Computer Tremor Score (ACTS) is based on spiral drawings on a graphic digitizing tablet. The aim of the study was to evaluate a new method and compare it with the standardized methods of tremor assessment. MATERIAL AND METHODS: A hundred and one patients with idiopathic Parkinson's disease (IPD) and 52 patients with essential tremor (ET) were examined. All subjects were asked to draw an Archimedes spiral on the graphic tablet. The drawn spirals were evaluated using ACTS and clinically by three independent raters according to a ten-point scale. Tremor was additionally assessed using the volumetric method. The Automated Computer Tremor Score correlated considerably with tremor rates provided by every rater (r=0.68 vs. r=0.76, p<0.0001), and with measures obtained using the volumetric method (r=0.63, p=0.01 and r=0.56, p= 0.03). ACTS also correlated with ADL score among ET patients (r=0.56, p=0.0004). CONCLUSIONS: The study shows that neuronal networks may be taught to rate tremor severity analogically to human rating and automated scoring may be a useful method in clinical practice.     

Bilaterally coherent tremor resembling enhanced physiological tremor: report of three cases.

The contribution of the central nervous system to tremor pathogenesis is unclear. Poor side-to-side coherence in physiological, essential, and parkinsonian tremors suggests distinct bilateral generators. By contrast, significant bilateral coherence demonstrated in orthostatic tremor and in enhanced physiological tremor (EPT) in patients with persistent mirror movements favours single or closely linked bilateral oscillators. We describe three patients (aged 21-37 years) who developed unusual bilateral postural and kinetic tremors at 6-13 Hz resembling EPT. The tremor involved all limbs, and in two cases the face or jaw, in the absence of other significant neurological features. Significant side-to-side coherence was demonstrated in each case using cross-correlation of electromyographic recordings from homologous muscle pairs. We postulate that these unusual tremors originate from a single brainstem source or from bilateral oscillators closely linked at or below this level.     

Relationship between amplitude of tremor and reflex response of the human jaw-closing system

Jaw-closing force was transduced while subjects maintained a biting force of 9.8 N. To estimate the amplitude of tremor in each subject's forces record, the average spectrum of the force was computed, and the definite integral of the averaged spectrum in the frequency range from 3.5 to 10 Hz was calculated. For the same sunjects, the amplitude of reflex responses to innocuous mechanical stimuli delivered to intraoral and perioral sites was measured as the peak-to-peak change in jaw-closing force following application of the stimulus. Force responses produced by stimulation at each site were used to compute an average reflex response measure for each subject. Large intersubject variability was observed in the amplitudes of jaw and reflex responses. A correlation coefficient computed between the tremor and reflex measures revealed that subjects with large amplitude tremor tended also to have a large reflex force responses. This correlation is consistent with the suggestion that activity in cutaneous reflex pathways contributes to tremor of the human mandible.     

Isometric features of orthostatic tremor: an electromyographic analysis

A patient is described with "orthostatic" tremor. Electromyography revealed tremor bursts of 15 Hz in the lower extremities while standing and with isometric activation of the muscles, but the bursts disappeared with isotonic activation of muscles. Similar tremor was recorded in the arms with isometric, but not isotonic activation. Review of previously reported cases confirms these findings. The clinical and electrophysiologic features of this tremor distinguish it from other recognized forms of tremor.     

The cerebral basis of Parkinsonian tremor: A network perspective

Tremor in Parkinson's disease is a poorly understood sign. Although it is one of the clinical hallmarks of the disease, its pathophysiology remains unclear. It is clear that tremor involves different neural mechanisms than bradykinesia and rigidity, the other core motor signs of Parkinson's disease. In particular, the role of dopamine in tremor has been heavily debated given clinical observations that tremor has a variable response to dopaminergic medication. From a neuroscience perspective, tremor is also a special sign; unlike other motor signs, it has a clear electrophysiological signature (frequency, phase, and power). These unique features of tremor, and newly available neuroimaging methods, have sparked investigations into the pathophysiology of tremor. In this review, evidence will be discussed for the idea that parkinsonian tremor results from increased interactions between the basal ganglia and the cerebello‐thalamo‐cortical circuit, driven by altered dopaminergic projections to nodes within both circuits, and modulated by context‐dependent factors, such as psychological stress. Models that incorporate all of these features may help our understanding of the pathophysiology of tremor and interindividual differences between patients. One example that will be discussed in this article is the “dimmer‐switch” model. According to this model, cerebral activity related to parkinsonian tremor first arises in the basal ganglia and is then propagated to the cerebello‐thalamo‐cortical circuit, where the tremor rhythm is maintained and amplified. In the future, detailed knowledge about the architecture of the tremor circuitry in individual patients (“tremor fingerprints”) may provide new, mechanism‐based treatments for this debilitating motor sign. © 2017 International Parkinson and Movement Disorder Society     

Development of an essential tremor embarrassment assessment

IntroductionEmbarrassment 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.MethodsBased 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.ResultsForty-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).ConclusionEmbarrassment is commonly experienced by ET patients. The ETEA is a reliable and valid tool to measure embarrassment in patients with this disease.     

Essential tremor - assessment of tremor accelerometric parameters' symmetry and the relationship between hand dominance and severity of tremor

Background and purposeEssential tremor (ET) is likely the most common movement disorder. The aim of the study was to carry out spectral analysis of the essential tremor recorded by an accelerometer and assess the symmetry of tremor parameters between the two hands.Material and methodsWe examined 39 patients with ET diagnosed clinically using the criteria of the Movement Disorder Society. The control group consisted of 52 healthy persons. A biaxial accelerometer mounted at the dorsal side of the hand was used. Spectral analysis was performed. Tremor intensity, frequency of spectral peaks, centre frequency, standard deviation of the centre frequency, and harmonic index were measured. The side-to-side symmetry of these parameters was analysed. The relationship of hand dominance and severity of tremor was also analysed.ResultsThere was significant side-to-side asymmetry of intensity in ET. The intensity in the more affected hand was over two times higher than that in the less affected one. The tremor was more severe in the nondominant hand in 62% of patients. In spite of significant difference in tremor intensity between the two sides, tremor frequency was similar in both hands. The standard deviation of centre frequency was significantly lower and the harmonic index was significantly higher in the more trembling hand.ConclusionsAccelerometric registration revealed that asymmetry of intensity and symmetry of frequency are characteristic features of ET. The remaining two coefficients reflecting the rhythmicity and regularity of tremor also differed considerably between the hands.     

Clozapine in the treatment of tremor

In an open trial 25 tremor patients were treated with clozapine in small doses (18-75 mg per day). The effect was measured with a new movement analyzer. Nine of 12 essential tremor patients were greatly improved. In six of nine patients with Parkinson tremor and in two combined essential tremor/Parkinson tremor patients tremor almost disappeared. Sedation is a major side effect, but decreases in most patients with time. The risk of agranulocytosis makes blood control necessary.