Interest in participating in clinical research: A study of essential tremor patients.

Enrolling essential tremor (ET) patients in clinical research can be challenging. Investigators can maximize recruitment by targeting patient subgroups with greater interest in participation. Nothing has been published on factors that are associated with higher levels of interest in participation. The objective of this study was to identify factors associated with higher levels of interest in participating in clinical research on ET. A total of 149 ET patients were questioned about level of interest in participating in future research. Two questions were used, although one was of primary interest. Interest was rated from 0 to 10 (maximal). Data were collected on demographic factors, family history, and tremor-related disability. Tremor severity was assessed. The mean level of interest was 8.0 +/- 2.3. Level of interest was not related to age of tremor onset, tremor duration, tremor severity, extent of tremor-related disability, or use of tremor medication. Level of interest was related to family history of tremor (P < 0.05), concern that other family members might develop tremor (P < 0.05), >2 versus 0 live births in women (P < 0.05), the view that the tremor worsens with age (P < 0.05), and presence of head tremor (P = 0.05). A variety of factors were identified that were associated with greater interest in participating in clinical research. These observations should be assessed in additional patient samples. Investigators may use our observations to identify and target patients for clinical trials and other research.     

Jaw tremor: prevalence and clinical correlates in three essential tremor case samples.

The spectrum of involuntary movements seen in essential tremor (ET) is limited. Jaw tremor is one such movement. The prevalence and clinical correlates of jaw tremor have not been studied in detail. The objective of this study was to estimate the prevalence and examine the clinical correlates of jaw tremor in ET using ET cases from three distinct settings (population, tertiary-referral center, brain repository). All ET cases underwent a videotaped tremor examination in which tremors (including limb, head, voice, and jaw) were assessed. The prevalence [95% confidence interval (CI)] of jaw tremor was lowest in the population sample (7.5%; 3.9%-14.2%), intermediate in the tertiary-referral center (10.1%; 6.8%-14.7%), and highest in the brain repository (18.0%; 12.3%-25.5%; P = 0.03). Jaw tremor was associated with older age (P < 0.001), more severe action tremor of the arms (P < 0.001), and presence of head and voice tremor (P < 0.001). Jaw tremor was present in 4/14 (28.6%) ET cases with consistent rest tremor vs. 15/193 (7.8%) cases without rest tremor (odds ratio = 4.8; 95% CI = 1.3-7.0; P = 0.009). The prevalence of jaw tremor was 7.5% to 18.0% and was dependent on the mode of ascertainment, being least prevalent in a population-based sample. ET cases with jaw tremor had a more clinically severe and more topographically widespread disorder. The association in our study between jaw tremor and rest tremor, along with the published observation that jaw tremor can occur in Parkinson's disease (PD), raises the question whether jaw tremor in ET is a marker for subsequent conversion to PD.     

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.     

Risk of incident dementia in essential tremor: a population-based study.

Essential tremor (ET) is a late-life neurological disease. Mild cognitive deficits as well as an association with prevalent dementia have been reported in recent case-control studies. We determined whether ET was associated with an increased risk of incident dementia. In a population-based study of older people in central Spain (NEDICES), nondemented ET cases and controls were followed prospectively. Incident dementia at follow-up was diagnosed using DSM-IV criteria and the risk of incident dementia was estimated in ET cases versus controls using Cox proportional hazards models. 3,891 participants had a mean duration of follow-up of 3.2 years. Sixteen (7.8%) of 206 ET cases developed incident dementia versus 145 (3.9%) of 3,685 controls (unadjusted relative risk [RR]=2.08, 95% CI=1.24-3.50, P=0.006 and adjusted RR=1.66, 95% CI=0.99-2.80, P=0.054). In an adjusted model, ET cases with tremor onset after age 65 years were twice as likely to develop incident dementia than were controls (RR=1.98, 95% CI=1.14-3.45, P=0.01), whereas ET cases with tremor onset相似文献   

Faster rate of cognitive decline in essential tremor cases than controls: a prospective study

Background: Mild cognitive deficits have been reported in essential tremor (ET). However, these cognitive deficits have been assessed in cross‐sectional rather than longitudinal analyses. Objective: To determine whether decline in cognitive test scores occurs at a faster rate in ET cases than controls. Methods: In a population‐based study of older people (≥ 65 years) in central Spain (Neurological Disorders in Central Spain, NEDICES), non‐demented ET cases and controls were followed prospectively. Participants with baseline or incident Parkinson’s disease or dementia were excluded as were participants who developed incident ET. At baseline (1994–1995) and at follow‐up (1997–1998), a 37‐item version of the mini‐mental state examination (37‐MMSE) was administered. Results: A total of 2319 participants (72.4 ± 5.8 years) included 135 prevalent ET cases and 2184 controls. At baseline, the mean 37‐MMSE in cases was 28.8 ± 5.8 vs. 30.2 ± 4.8 in controls (P = 0.02). During the 3‐year follow‐up period, the 37‐MMSE declined by 0.70 ± 3.2 points in cases vs. 0.11 ± 3.8 points in controls (P = 0.03). In analyses that adjusted for age, education, and other potential confounders, the case–control difference remained robust. Discussion: In this population‐based, prospective study of non‐demented elders, baseline cognitive test scores were lower in ET cases than controls; moreover, during the 3‐year follow‐up period, these scores declined at a rate that was seven‐times faster in ET cases. This study provides evidence that cognitive deficits in ET are not static, and they appear to be progressing at a faster rate than in elders without this disease.     

Deep brain stimulation for essential tremor: A systematic review

Deep brain stimulation (DBS) is a neurosurgical treatment, which has proven useful in treating Parkinson's disease. This systematic review assessed the safety and effectiveness of DBS for another movement disorder, essential tremor. All studies concerning the use of DBS in patients with essential tremor were identified through searching of electronic databases and hand searching of reference lists. Studies were categorized as before/after DBS or DBS stimulation on/off to allow the effect of the stimulation to be analyzed separately to that of the surgery itself. A total of 430 patients who had received DBS for essential tremor were identified. Most of the reported adverse events were mild and could be treated through changing the stimulation settings. Generally, in all studies, there was a significant improvement in outcomes after DBS compared with baseline scores. In addition, DBS was significantly better in testing when the stimulation was turned on, compared with stimulation turned off or baseline. Based on Level IV evidence, DBS is possibly a safe and effective therapy for essential tremor. © 2010 Movement Disorders Society     

Orthostatic tremor: essential and symptomatic cases

We studied clinically and electrophysiologically 8 patients affected by orthostatic tremor (OT), which is an unusual movement disorder consisting of shaking movements of the legs and trunk in the standing position. We failed to find any cause in 6 of the 8 cases. In 2 patients OT was clearly secondary to neurologic disease: hydrocephalus due to non-tumoral aqueduct stenosis and chronic relapsing polyradiculoneuropathy. The findings obtained suggest a relationship between OT and essential tremor (ET).     

Factors associated with increased risk of head tremor in essential tremor: a community-based study in northern Manhattan.

Head tremor is one of the major expressions of essential tremor (ET). It is not well understood why some patients develop head tremor, whereas others do not. A study of the characteristics of patients with head tremor has not been undertaken. Our goal was to estimate the prevalence of head tremor and to identify demographic and clinical characteristics associated with an increased risk of head tremor in ET. Cases were ascertained from a community-based study of ET in northern Manhattan, New York. Arm tremor severity was rated with a total tremor score. Logistic regression analyses resulted in odds ratios (OR). Head tremor was present in 37 (34.9%) of 106 ET cases. Female gender was associated with a fourfold increased risk of head tremor (OR = 3.73; P = 0.005). Total tremor score was divided into quartiles; individuals in the lowest or highest quartile were four times more likely to have head tremor (OR = 4.16; P = 0.001). Individuals with both risk factors (female gender and lowest or highest total tremor score quartile) were 16 times more likely to have head tremor (OR = 15.88; P = 0.0006). Being related to a proband with head tremor marginally increased the risk of head tremor (OR = 11.30; P = 0.08). Age and tremor duration did not influence the risk of head tremor. We identified several factors that were associated with an increased risk of head tremor in ET; female gender, coexisting arm tremor that was either very mild or extremely severe, and relation to an ET case with head tremor. These disease associations require further exploration, and might provide insight into the mechanisms underlying head tremor.     

Unusual forehead tremor in a patient with essential tremor.

Voice and head (neck) tremor commonly occur in patients with essential tremor (ET), but involvement of cranial musculature is generally limited to these specific cranial structures, and action tremor of the forehead has not been reported. We describe a patient with ET who had forehead tremor. The tremor seemed to be task-specific, and neurophysiological features suggested that the forehead tremor was dystonic. The presence of forehead tremor in a patient with ET probably indicates an additional pathophysiologic process. The explanation for the specificity of involvement of cranial musculature in ET is not known, but this clinical observation might help guide investigators who are interested in the underlying pathophysiology of this condition.     

Pilot efficacy and tolerability: a randomized, placebo-controlled trial of levetiracetam for essential tremor.

The purpose of this pilot single-site study was to assess efficacy and safety of levetiracetam for essential tremor, using a placebo-controlled, double-blind, randomized crossover design with an interim analysis planned after completion of the first 10 to 15 subjects. The study was designed to detect a mean 30% reduction in composite tremor score, comparable to that of primidone or propranolol, which can be demonstrated with 30 or fewer subjects. Each treatment arm included baseline tremor assessments, a 4-week medication titration, 2 weeks of stable dose, and treatment tremor assessments. Levetiracetam was titrated to 3,000 mg/day or to a lower maximal tolerated dose. The median age was 72 years, with 28 years median tremor duration. There was no statistically significant difference in response between placebo and levetiracetam on any tremor rating scale or accelerometry measure. The 95% confidence interval for the true mean difference between placebo and levetiracetam treatments was +18.5 to -22.5%, which excludes the minimum 30% drop required to consider levetiracetam clinically effective to a degree comparable to primidone or propranolol. Whether levetiracetam has lesser-degree antitremor efficacy was not addressed in this pilot study.     

特发性震颤的临床特点分析

目的探讨特发性震颤(essential tremor,ET)的临床特点。方法对92例ET患者的临床资料进行回顾性分析。结果92例ET中男58例,女34例,发病年龄12～80岁,平均(50.2±17.3)岁,病程6个月～60年,平均(16.2±8.9)年。49例(53.3%)患者有阳性家族史,多呈常染色体显性遗传,临床主要表现为单症状的姿势性震颤,累及部位依次为手(92.4%)、头(25.0%)、咽喉部(21.7%)、下颏(15.2%)等。16.3%患者因震颤致日常生活困难。42例饮酒患者中,85.7%显示对酒精有反应性。6.5%患者并发帕金森病(Parkinson’s disease,PD)。67.3%患者小剂量普萘洛尔治疗有效。结论本组ET患者男多于女,临床表现为单症状姿势性震颤,部分病例可伴发PD,小剂量普萘洛尔治疗大多有效。     

Increased risk of head tremor in women with essential tremor: longitudinal data from the Rochester Epidemiology Project.

In one cross-sectional study of a community in northern Manhattan, women with essential tremor (ET) were more likely to have head tremor than were men. In that study, patients were seen at one point in time, rather than followed longitudinally. Head tremor often develops after arm tremor, and its appearance in patients with ET may therefore be a function of duration of follow-up. In a second epidemiological study utilizing the Rochester Epidemiology Project, in which ET subjects were followed from disease diagnosis to death, we determined whether there was an association between female gender and head tremor. We utilized the records-linkage system of the Rochester Epidemiology Project to identify ET cases. Records were reviewed and clinical data abstracted by a neurologist specializing in movement disorders. A second neurologist reviewed a subsample of records. There were 107 ET cases (69 women, 38 men) followed for 10.1 +/- 9.1 years from ET diagnosis to death. Head tremor was present in 37 (53.6%) women and 5 (13.2%) men (odds ratio [OR] = 7.6, 95% confidence interval [CI] = 2.7-21.9, P < 0.001). In a multivariate linear regression analysis, women remained at high risk for head tremor (OR = 6.5, 95% CI = 2.2-19.0, P = 0.001) independent of disease duration. We found in this longitudinal epidemiological study that women with ET were six times more likely to develop head tremor over the course of their illness than were men. The reason for the association between gender and head tremor, which has now been demonstrated in several studies, is not known, but it could reflect gender differences in the distribution of disease pathology within the brain.     

Subclinical tremor in normal controls with versus without a family history of essential tremor: data from the United States and Turkey

Background and purpose: Mild action tremor is very common in the population. One fundamental question is whether this tremor is related to the neurological disease essential tremor (ET), which occurs in a much smaller segment of the population? ET is often genetic, and variable phenotypic expression is well‐documented in the literature. We determined whether normal controls who report a family history of ET have greater action tremor than normal controls who do not report such a history. Methods: Controls, enrolled in two epidemiological studies (New York and Turkey), were examined in detail and action tremor was rated using a valid and reliable clinical rating scale, resulting in a total tremor score (range 0–36). Results: In New York, the total tremor score was higher in 44/406 (10.8%) controls who reported a family history of ET than in 362/406 controls with no such history (4.25 ± 2.51 vs. 3.78 ± 2.93, P = 0.02). Controls who reported a first‐degree relative with ET had the highest total tremor scores. In Turkey, the total tremor score was higher in 7/89 (7.9%) controls with a family history than in 82/89 controls with no family history (3.43 ± 4.54 vs. 1.13 ± 2.54, P = 0.048). All affected relatives in Turkey were first‐degree. Conclusions: These data suggest that some of the normal tremor exhibited by people in the population is likely to be subclinical, partially expressed ET and that the sphere of ET is wider than is apparent from a consideration of clinically diagnosed cases.     

Report from a U.S. conference on essential tremor.

Seventy researchers met in Washington, DC, on 20-21 October 2005 to identify and discuss the most pressing research issues in essential tremor (ET). The conference attendees concluded that the following six objectives are of immediate and overriding importance: (1) a collaborative network of research centers; (2) an international committee for developing a standard protocol for the diagnosis and quantification of ET; (3) the identification of one or more genes for ET; (4) a centralized repository of DNA and, ideally, immortalized cell lines from well-characterized ET families and healthy controls; (5) a reliable and efficient repository of optimally prepared and categorized brain samples for hypothesis-driven neuropathological examinations in well-characterized ET patients; and (6) animal models of ET for screening promising drugs. The conference attendees hope that this statement from the United States will engender international collaboration in finding a cure for ET.