Rest tremor in patients with essential tremor: prevalence, clinical correlates, and electrophysiologic characteristics.

BACKGROUND: Isolated rest tremor, which is observed in some patients with essential tremor (ET), poses a diagnostic challenge. The phenomenon has been examined in few studies and is poorly understood. OBJECTIVES: To determine the prevalence and study the clinical correlates of rest tremor in ET and to examine the electrophysiologic features in a subgroup of patients. METHODS: Sixty-four patients with ET cared for at a tertiary referral center underwent neurologic examination. Five of 12 patients with rest tremor also underwent quantitative computerized tremor analysis using accelerometry and handwritten spiral analysis. RESULTS: Twelve of 64 patients with ET had rest tremor (prevalence, 18.8%; 95% confidence interval, 9.2%-28.4%). Compared with the 52 patients with ET without rest tremor, these 12 had disease of longer duration and greater severity. Also, their ET was more widely disseminated, as evidenced by a larger proportion with head tremor. None had clinical signs of bradykinesia or rigidity. The 5 patients with rest tremor who underwent electrophysiologic study had electrophysiologic features consistent with parkinsonism (eg, slow spiral speed and increased decrement of spiral speed with radius). CONCLUSIONS: In our sample, 1 in 5 patients with ET had rest tremor. The tremor was associated with disease that was more severe, more disseminated, and of longer duration. Some of these patients had electrophysiologic features consistent with parkinsonism. The basis for the rest tremor could be basal ganglia involvement, raising the possibility that the pathologic process responsible for ET may extend to these structures.

Body mass index in essential tremor.

BACKGROUND: The pathogenesis of essential tremor (ET) is unknown, but it could be neurodegenerative. Weight loss has been observed in patients with neurodegenerative diseases. OBJECTIVES: To compare body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) in ET cases and controls and to determine whether BMI is correlated with tremor severity and duration. METHODS: Patients with ET were ascertained from the Neurological Institute of New York, New York, NY. Control subjects were recruited from 2 studies at the same institution. Height and weight were measured and BMI was calculated. Dietary data were collected using a Willett Semi-Quantitative Food-Frequency Questionnaire. Tremor severity was assessed using a clinical scale and the Klove Matthews Motor Steadiness Battery. RESULTS: The 78 cases and 242 controls were of similar age. Mean (SD) BMI in cases vs controls was 26.5 (5.0) vs 28.2 (4.8) (P =.008). This difference remained significant in an unconditional linear regression analysis that adjusted for age, sex, ethnicity, and years of education (P =.02). Mean daily caloric intake was similar in cases and controls. In cases, BMI was negatively correlated with both measures of tremor severity (r = -0.22; P =.05 and r = -0.24; P =.03) and with tremor duration (r = -0.22; P =.05). CONCLUSIONS: The BMI was lower in ET cases than in controls, and lower BMI was associated with disease of greater severity and longer duration. Caloric intake did not differ between groups, suggesting that lower BMI is not due to a reduction in calories. Lower BMI may be due to increased energy expenditure in ET.

Olfactory dysfunction in essential tremor: a deficit unrelated to disease duration or severity.

Because olfactory dysfunction is a feature of neurodegenerative diseases, the authors hypothesized that it would be present in essential tremor. Thirty-seven cases and control subjects underwent the University of Pennsylvania Smell Identification Test. Mean score was lower in cases than in control subjects (29.0 +/- 6.1 vs 31.9 +/- 4.6, p = 0.02) and was not correlated with tremor severity or duration.

Association between essential tremor and blood lead concentration.

Lead is a ubiquitous toxicant that causes tremor and cerebellar damage. Essential tremor (ET) is a highly prevalent neurologic disease associated with cerebellar involvement. Although environmental toxicants may play a role in ET etiology and their identification is a critical step in disease prevention, these toxicants have received little attention. Our objective was to test the hypothesis that ET is associated with lead exposure. Therefore, blood lead (BPb) concentrations were measured and a lifetime occupational history was assessed in ET patients and in controls. We frequency matched 100 ET patients and 143 controls on age, sex, and ethnicity. BPb concentrations were analyzed using graphite furnace atomic absorption spectrophotometry. A lifetime occupational history was reviewed by an industrial hygienist. BPb concentrations were higher in ET patients than in controls (mean +/- SD, 3.3 +/- 2.4 and 2.6 +/- 1.6 microg/dL, respectively; median, 2.7 and 2.3 microg/dL; p = 0.038). In a logistic regression model, BPb concentration was associated with diagnosis [control vs. ET patient, odds ratio (OR) per unit increase = 1.21; 95% confidence interval (CI), 1.05-1.39; p = 0.007]. BPb concentration was associated with diagnosis (OR per unit increase = 1.19; 95% CI, 1.03-1.37; p = 0.02) after adjusting for potential confounders. Prevalence of lifetime occupational lead exposure was similar in ET patients and controls. We report an association between BPb concentration and ET. Determining whether this association is due to increased exposure to lead or a difference in lead kinetics in ET patients requires further investigation.

Metabolic abnormality in the cerebellum in patients with essential tremor: a proton magnetic resonance spectroscopic imaging study.

The pathological basis for essential tremor (ET) is unknown. We used proton magnetic resonance spectroscopic imaging (1H MRSI) in 16 ET patients and 11 controls to measure levels of intracellular metabolites, including N-acetyl-L-aspartate (NAA) and total choline, relative to total creatine (tCR), in several brain regions (cerebellum, thalamus, basal ganglia). Multislice 1H MRSI data were acquired on a 1.5 T GE Signa Scanner by prescribing four 15-mm axial-oblique slices. The mean (standard deviation) cerebellar cortical NAA/tCR was reduced in cases compared to controls (1.53 [0.36] versus 1.91 [0.49], P = 0.03). There was an inverse association between cerebellar cortical NAA/tCR and dominant arm tremor severity (r = -0.59, P = 0.02). The reduction in cerebellar cortical NAA/tCR indicates that there is neuronal damage or loss in ET, suggesting that ET may be a neurodegenerative disease.

Improved psychological status in a modified therapeutic community for homeless MICA men.

An adaptation of the drug-free therapeutic community (TC) model to homeless men with comorbid mental illness and chemical addiction (MICA) was evaluated with respect to change in psychological status over the course of a six-month residential treatment. Psychological status was assessed by: the Symptom Checklist-90-R (SCL90-R), Beck Depression Inventory (BDI), Shortened Manifest Anxiety Scale (SMAS), and Tennessee Self-Concept Scale (TSCS). A total of 52 out of an original study cohort of 124 residents were followed in longitudinal analyses to treatment midpoint, with a subset of 34 assessed through treatment completion. Significant, widespread psychological improvements were found during both the first and second half of treatment; it would appear that distress reduction was ongoing throughout treatment, with intrapersonal preceding interpersonal relief. The premise of applying a socially-based treatment to this population is discussed in light of these findings.

Case-control study of nutritional antioxidant intake in essential tremor.

The theory that oxidative stress is involved in the pathogenesis of neurodegenerative diseases has received considerable attention and studies have linked these diseases to the diminished use of antioxidant vitamins (vitamins E and C) and other dietary antioxidants. Essential tremor (ET) is a chronic, progressive disease. One possible disease mechanism is neurodegenerative. Whether nutritional antioxidant use differs between ET cases and controls is not known. Using a case-control design, we conducted detailed dietary assessments and tested the hypothesis that diminished use of nutritional antioxidants is associated with ET. Data on diet were collected on 156 ET cases and 220 controls using a semi-quantitative food-frequency questionnaire. There was no evidence that current nutritional antioxidant exposure differs in ET cases and controls. This does not exclude the possibility that nutritional antioxidant exposure was lower in ET cases prior to their disease onset.

Olfaction in essential tremor patients with and without isolated rest tremor.

An olfactory deficit is present in patients with essential tremor (ET), but it is often milder than that in patients with Parkinson's disease (PD). In both, the deficit occurs early in the disease. Isolated rest tremor without other signs of parkinsonism can occur in patients with ET. If the rest tremor in these patients represents a manifestation of ET rather than early PD, we hypothesized that their University of Pennsylvania Smell Identification Test (UPSIT) scores would be similar to those of ET patients without rest tremor. The mean UPSIT score in 13 ET patients with isolated rest tremor did not differ from that of 58 ET patients without rest tremor (29.3 +/- 4.3 vs. 29.4 +/- 6.4; P = 0.69). Several ET patients with rest tremor had UPSIT scores that fell outside of the range that is seen in 95% of patients with PD. These data raise the possibility that some ET patients with isolated rest tremor may not have early PD and that the pathological process that is responsible for their ET is also involving the basal ganglia.

Community-based data on associations of disease duration and age with severity of essential tremor: implications for disease pathophysiology.

The pathophysiology of essential tremor (ET) is not well understood, although the tremor often worsens over time. Several processes could contribute, including the inherent worsening of the underlying disease with increasing disease duration and the effects of aging on the nervous system. Our objective was to examine the associations of disease duration and age with tremor severity in ET. Cases were ascertained from a community-based study of ET in northern Manhattan, New York. A neurologist rated tremor severity using a clinical rating scale and assigned a total tremor score (0-36 [maximum]). Analyses were repeated in a sample of cases from a tertiary referral center, the Neurological Institute of New York. There were 55 cases from the community-based study (mean age, 72.1 years, mean disease duration, 13.2 years). Disease duration was associated with the total tremor score (r = 0.30; P = 0.02). Age was associated with the total tremor score (r = 0.30; P = 0.025). In a linear regression analysis the dependent variable was the total tremor score and independent variables were disease duration, age gender. Duration (beta = 0.11; P = 0.02) and age (beta = 0.10; P = 0.02) were independently associated with the total tremor score. Results were similar in 79 ET cases from the Neurological Institute. Disease duration and age were independently associated with tremor severity in ET. This suggests that the reported increase in tremor severity may be related to the inherent worsening of the disease with increasing duration that this is independent of age and age-related processes like neuronal attrition and change in tremor frequency.

Survey of essential tremor patients on their knowledge about the genetics of the disease.

A group of essential tremor (ET) patients were surveyed on their knowledge of the genetics of ET in order to provide important information to clinicians who care for and educate patients about this disease. ET patients were ascertained from neurologists at Columbia-Presbyterian Medical Center. A 5- to 10-minute survey was administered to assess knowledge of the genetics of ET. Fifty ET patients had been living with their disease for a mean of 24.2 years. Approximately half (n = 27) reported a family history of ET. When asked, "What causes ET," 12 (24%) replied that it was "hereditary." Even among the 27 who reported a family history, only 25.9% replied that it was "hereditary." A minority of patients (12 [24%]) thought that it was "very likely" that other members of their family would develop the disease some day. Three patients were aware that genetic linkage had been established. Our findings suggest that the majority of patients with ET are not well informed about the genetic basis for the disease. Because of recent advances in genetic research, physicians may need to incorporate more genetic information and education into their practice, including information on risk to other family members and genetic testing. It is hoped that these survey results could be used to improve patient education and to provide clinicians with further insight into patients' perspectives.

Cerebellar metabolic symmetry in essential tremor studied with 1H magnetic resonance spectroscopic imaging: implications for disease pathology.

The pathological basis for essential tremor (ET) is not known; however, metabolic changes in the cerebellum can be observed in positron emission tomography (PET) and (1)H magnetic resonance spectroscopic imaging (MRSI) studies. Tremor is relatively symmetric in ET, suggesting that underlying metabolic changes could be also symmetric. The degree of metabolic asymmetry in the cerebellum, however, has not yet been studied in ET, and knowledge about distribution and laterality of metabolic changes might shed some light on basic disease mechanisms. We measured brain metabolism (N-acetylaspartate[NAA]/creatine [tCR]) to obtain an asymmetry index for cerebellar cortical metabolism ET patients compared with that in controls. This index, a percentage, was calculated as [absolute value (value right - value left)]/(value right + value left) x 100. Multislice (1)H MRSI data were acquired for 20 patients and 11 controls. In ET patients, mean right and left cerebellar cortical NAA/tCR values were 1.61 +/- 0.42 and 1.55 +/- 0.38, respectively, compared with 1.81 +/- 0.62 and 1.87 +/- 0.49 in controls. The difference between right and left cerebellar cortical NAA/tCR was also calculated for each subject. In ET patients, the mean right-left difference was 0.14 +/- 0.11, compared with 0.32 +/- 0.27 in controls (P = 0.016). The mean cerebellar cortical asymmetry index was low in ET (8.8 +/- 6.1%), one-half of that in controls (17.0 +/- 13.7%, P = 0.027). These data suggest that pathological lesions in ET patients, which remain elusive, might be distributed similarly in each cerebellar cortex. Postmortem studies are needed to confirm these preliminary imaging results.

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.

Semiquantitative study of current coffee, caffeine, and ethanol intake in essential tremor cases and controls.

There are several reasons to study caffeine, coffee, and ethanol intake in essential tremor (ET) patients. ET patients also might modify their use of these beverages because of their effects on tremor. Intake of caffeine, coffee, and ethanol has not been quantified in a group of ET patients. Our objective is to use a semiquantitative food frequency questionnaire to compare current daily intake of coffee, caffeine, and ethanol in ET patients and controls. A total of 130 ET cases were patients at the Neurological Institute of New York, and 175 controls were ascertained by random digit dialing. Caffeine (in milligrams) and ethanol (in grams) intake were calculated from a semiquantitative food-frequency questionnaire. Mean daily caffeine intake in patients was 138.4 versus 246.6 mg in controls; medians were 101.1 versus 175.5 mg (P < 0.001). Mean daily ethanol intake in patients was 8.2 versus 6.2 gm in controls; medians were 2.4 versus 1.9 gm (P = 0.89). Cases drank less coffee than controls, but drank similar amounts of tea, soft drinks, fruit juices, and milk. Daily caffeine intake was not correlated with tremor severity or duration. ET patients consumed less caffeine than did controls, which is likely to be a dietary modification in response to tremor. The observation that caffeine consumption was not correlated with tremor severity raises the additional possibility that lower caffeine consumption in ET patients may not exclusively be a response to tremor. A prospective study is needed to explore whether decreased caffeine consumption is a risk factor for ET.