Risk of tremor and impairment from tremor in relatives of patients with essential tremor: a community-based family study.

Essential tremor (ET) is a common condition that is present in as many as 23% of elderly individuals. Our objective was to determine the risk of ET and to study the impairment resulting from ET among relatives of ET cases compared to relatives of controls. ET cases and matched controls from the Washington Heights-Inwood community, New York, and their first- and second-degree relatives underwent a standardized tremor examination. The risk of having ET in relatives of cases vs relatives of controls was compared using Cox proportional hazards models. Five hundred ninety-one subjects were examined (59 ET cases, 72 controls, 234 case relatives, and 226 control relatives). ET was present in 25 (22.5%) of the 111 first-degree relatives of cases compared to 6 (5.6%) of 107 first-degree relatives of controls [relative risk (RR) = 4.67, 95% confidence interval (CI) = 1.90-11.49, p = 0.0008]. RRs were higher in relatives of cases with onset < or =50 years than in those with later onset (RR = 10.38 vs 4.82). Sixteen (64%) of twenty-five affected first-degree case relatives exhibited moderate tremor while performing tasks such as writing, drinking, or pouring. Relatives of ET patients are five times more likely to develop the disease than are members of the population and ten times more likely if the proband's tremor began at an early age. The majority of the affected relatives can expect to experience impairment resulting from tremor.

Characteristics of social phobia among persons with essential tremor.

BACKGROUND: Social phobia symptoms have been reported to be common among patients with essential tremor, but characteristics of this comorbidity have not been systematically described. METHOD: Cases with essential tremor (N = 94) and controls without essential tremor (N = 85), ascertained from movement disorder clinic and community samples, were evaluated for social phobia symptoms (using the social phobia module of the Structured Clinical Interview for DSM-IV Axis I Disorders and the Liebowitz Social Anxiety Scale), characteristics of tremor, and associated disability (via videotaped examination, performance test, and disability questionnaire). RESULTS: Lifetime combined prevalence of primary social phobia and clinically significant social phobia symptoms occurring secondary to essential tremor was 32.7% (16/49) among essential tremor patients in the clinic sample. Essential tremor cases with secondary social phobia symptoms reported a markedly later age at onset of clinically significant social phobia symptoms than essential tremor cases with primary social phobia (51.0 vs. 8.8 years). Cases with secondary social phobia also reported greater fear and avoidance of eating, drinking, and writing in public than essential tremor cases with primary social phobia and control subjects with social phobia. Essential tremor cases with secondary social phobia symptoms also demonstrated more severe tremor and tremor-related disability than essential tremor cases with primary social phobia and essential tremor cases without social phobia. Among all essential tremor cases, severity of social phobia symptoms and tremor independently contributed to disability. CONCLUSION: Social phobia appears to occur in a substantial minority of essential tremor patients, and severity of social phobia symptoms is associated with disability, independent of tremor severity. Persons with social phobia symptoms secondary to essential tremor evidence clinical characteristics that differ from those of persons with primary social phobia. Further research is needed to determine the efficacy of treatment of social phobia in essential tremor patients with significant social phobia symptoms.

Family history information on essential tremor: potential biases related to the source of the cases.

The proportion of essential tremor (ET) cases that can be attributed to genetic factors is unknown; estimates range from 17--100%. One possible reason for this variability is that clinic and community cases may differ with regard to family history of ET. This is because clinic patients are self-selected and represent as few as 0.5% of all ET cases. Our goal was to determine whether ET cases ascertained from a clinic differed from those ascertained from a community in terms of the family history information that they provided. Subjects (57 clinic, 64 community) underwent a family history interview. Clinic cases were 4.73 times more likely to report an affected relative than were community cases. We conclude that there was a substantial difference between our clinic and community ET cases in terms of the information they provided regarding their family history. Selection and reporting biases could have accounted for this difference. Because of these biases, the source of the cases must be taken into consideration when investigators are trying to synthesize the widely variable results of studies that have estimated the genetic contribution to ET.

Clinical subtypes of essential tremor.

BACKGROUND: There is clinical variability in essential tremor (ET), but it is not clear whether this variability is because of the existence of distinct clinical subtypes of ET (ie, forms of ET that may differ in their etiology, rate of progression, or response to treatment). OBJECTIVES: To examine in a group of ET cases the age of onset, anatomic distribution, and rate of progression of tremor, and to look for associations between these factors. METHODS: Cases of ET were ascertained from a community (n = 60) and a tertiary referral clinic (n = 55) in northern Manhattan, New York, NY. All subjects underwent an interview and videotaped tremor examination. Rate of progression was estimated based on the tremor severity and reported disease duration at the time of evaluation. RESULTS: Age of onset was bimodally distributed in clinic cases. There were differences in the anatomic distribution of the tremor (arm tremor only vs head and arm tremor vs isolated head tremor). Rate of progression was distributed exponentially; there was a large cluster of subjects with slower rates of progression, and a smaller number who had faster rates. There was an association between age of onset and rate of progression (r = 0.46-0.50, P<.002); cases with older age of onset (>60 years) progressed more rapidly (P<.001). In addition, upper limb tremor progressed more slowly among those with concomitant head tremor (P =.03). CONCLUSIONS: Essential tremor is not a homogeneous condition. There are differences in age of onset, anatomic distribution of tremor, and rate of progression. The ET in several groups of patients in this study (those with age of onset >60 years and those without head tremor) progressed more rapidly, suggesting that these ET cases may define distinct clinical subtypes. These subtypes should be further assessed for etiologic and genetic heterogeneity as well as differences in responsiveness to therapeutic agents. Arch Neurol. 2000;57:1194-1198

Validity and test-retest reliability of a disability questionnaire for essential tremor.

BACKGROUND: One important outcome in clinical trials is patients' own opinions about whether the medication alleviates their symptoms and improves their ability to function. A valid and reliable method with which to assess this subjective information is important. OBJECTIVE: To determine the validity and test-retest reliability of the Columbia University Disability Questionnaire for Essential Tremor (ET). METHODS: Patients with ET underwent a 2.5-hour evaluation, including a 36-item tremor disability questionnaire, to assess the functional impact of tremor, a 26-item videotaped tremor examination rated by a neurologist, a 15-item performance-based test, and quantitative computerized tremor analysis. We determined the validity and test-retest reliability of the tremor disability questionnaire. Correlations between variables were assessed using Pearson's correlation coefficients and test-retest reliability with the weighted kappa statistic. RESULTS: Ninety-five patients with ET participated. The score on tremor disability questionnaire correlated with the neurologist's clinical ratings (r = 0.57, p <0.001) and the total score on the performance-based test (r = 0.69, p < 0.001). Correlations with quantitative computerized tremor analysis results were less robust, but each remained significant, including mean amplitude of dominant arm tremor while arms were extended (r = 0.56, p <0.001), while drawing a spiral (r = 0.42, p = 0.01), and while pouring (r = 0.34, p = 0.04). The questionnaire was readministered to 32 subjects, and the test-retest reliability was substantial (weighted kappa = 0.67). CONCLUSIONS: This Tremor Disability Questionnaire demonstrated substantial reliability, and it correlated with multiple measures of tremor severity, including a neurologist's clinical ratings, a performance-based test of function, and quantitative computerized tremor analysis results. The questionnaire would be useful in clinical trials in which it could be used as a reliable and valid tool to assess disability in ET.

Ethnic differences in essential tremor.

BACKGROUND: Ethnic differences in the clinical characteristics (severity and distribution) of essential tumor (ET) have not been studied. The presence of these differences suggests that ET is not a homogeneous disease and that there is variability in disease expression under different circumstances. As part of a community-based study, we evaluated a multiethnic group of cases. OBJECTIVE: To assess whether there are ethnic differences in the clinical characteristics of ET. METHODS: Elderly residents of Washington Heights-Inwood, New York, were enrolled in a community-based health study (N = 2117). Participants underwent a medical interview and a neurological examination conducted by a neurologist, and subjects with ET were identified. These subjects with ET were then enrolled in a community-based study of ET and underwent a tremor interview, a videotaped tremor examination, and in some cases, a performance-based test of function and quantitative computerized tremor analysis. A total tremor score (range, 0-36, with 0 indicating no tremor and 36 indicating maximum tremor) was assigned to each subject based on 2 neurologists' ratings of the tremor examination. RESULTS: Among 62 subjects with ET (white [n = 16], African American [n = 18], and Hispanic [n = 28]), there were ethnic differences in the total tremor score (F = 3.68, P = .03). In a multiple regression model adjusting for age, white subjects had a mean total tremor score that was 5.3 points lower than that of nonwhite subjects (P = .008). We divided the nonwhite group into African American and Hispanic subgroups. In a regression model adjusting for age and duration, the white group had a mean total tremor score that was 6.1 points lower than that of the Hispanic group (P = .07) and 7.2 points lower than that of the African American group (P = .05). The mean performance-based test score was 1.7 times higher in the African American group and 2.1 times higher in the Hispanic group compared with the white group (P = .38). No subjects in the African American group had head tremor, while 4 subjects in the white group (25%) and 8 subjects in the Hispanic group (29%) did have head tremor (chi2 = 6.17, P = .05). CONCLUSIONS: There are ethnic differences in the expression of ET, suggesting that ET is not a homogeneous disorder. These differences may reflect phenotypic variability caused by genotypic differences or differences in exposure to environmental factors that influence tremor.

Determination of harmane and harmine in human blood using reversed-phased high-performance liquid chromatography and fluorescence detection.

A number of tremorogenic beta-carboline alkaloids have been found in common plant-derived foodstuffs, beverages, and inhaled substances. Because of their natural presence in the food chain, there is a growing concern regarding the potential risks of certain essential tremors associated with the long-term, low-level dietary exposure to these alkaloids. The purpose of this study was to develop an effective analytical method to determine blood levels of two major beta-carboline derivatives, harmane and harmine. Human blood was extracted with ethyl acetate and methyl-t-butyl ether (2:98) under an alkaline condition. After evaporation of organic solvent, the samples were reconstructed in methanol. The samples were fractionated on a 250 x 4.6-mm C18 reversed-phase column with an isocratic mobile system consisting of 17.5 mM potassium phosphate buffer (ph 6.5) and methanol (30:70), followed by an on-line fluorescence detection. The method had the detection limit to determine 206 and 81 pg/ml of harmane and harmine, respectively, in 10 ml of human blood. The intraday precision (C.V.) at 25 ng/ml was less than 6.7 and 3.4% for harmane and harmine, respectively. The interday precision was 7.3% for harmane and 5.4% for harmine. The method has proven sensitive, reproducible, and thus useful for both laboratory and clinical studies of beta-carboline toxicities.

Validation of a portable instrument for assessing tremor severity in epidemiologic field studies.

BACKGROUND: An important part of epidemiologic and genetic studies of essential tremor (ET) is an assessment of tremor severity. Clinical rating scales are semiquantitative and computerized tremor analysis, available at tertiary medical centers, is not transportable into the field. As part of an epidemiologic study, we modified the Klove-Matthews Motor Steadiness Battery, collecting objective quantitative data on tremor severity in patients with ET and control subjects. OBJECTIVE: To describe the modified Klove-Matthews Motor Steadiness Battery, validate this test battery against several other measures of tremor severity, demonstrate test-retest reliability, and provide standard reference values for normal control subjects and patients with ET who undergo this test battery. METHODS: Patients with ET and control subjects, ascertained from both a clinic and a community, underwent a standardized evaluation including a demographic and medical questionnaire, tremor disability questionnaire, videotaped tremor examination, performance-based test, modified Klove-Matthews Motor Steadiness Battery (Groove-Type Steadiness Tester [GTST] and Nine-Hole Steadiness Tester [NHST]), and quantitative computerized tremor analysis. RESULTS: There were 19 patients with ET and 28 control subjects. NHST and GTST total scores were correlated significantly with the tremor disability questionnaire score (r = 0.63, p = 0.001 and r = 0.49, p = 0.016), total tremor score (tremor examination, r = 0.68, p<0.001 and r = 0.41, p = 0.005), performance-based test score (r = 0.81, p<0.001 and r = 0.65, p = 0.001), and quantitative computerized tremor analysis results (for example, spiral drawing, r = 0.62, p = 0.01 and r = 0.58, p = 0.019). Test-retest reliability was generally high (r = 0.79-0.94, p<0.001). CONCLUSION: The modified Klove-Matthews Motor Steadiness Battery provides a reliable and valid means to collect objective quantitative data on tremor severity. Rapidity of administration and ease of transport make it a potentially useful tool in epidemiologic and genetic field studies.