Eva C. Jurewicz

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.

Elevation of blood β-carboline alkaloids in essential tremor

Background: β-Carboline alkaloids are normal body constituents but are also potent tremor-producing chemicals that are naturally present in the food chain. Objective: To explore the hypothesis that high concentrations of β-carboline alkaloids are associated with essential tremor (ET). Methods: One hundred cases and 100 controls were frequency matched on age, sex, and ethnicity. Blood concentrations of harmane and harmine were quantified by high-performance liquid chromatography, blinded to clinical information. Results: The mean log blood concentration of harmane was higher in cases than controls (0.72 ± 0.53 vs 0.51 ± 0.64 g−10/mL; p = 0.01). A nonparametric test on nontransformed data (median harmane = 5.21 g−10/mL in cases and 2.28 g−10/mL in controls) confirmed this difference (p = 0.005). The mean log blood concentration of harmine was 0.20 ± 0.48 g−10/mL in cases and 0.10 ± 0.65 g −10/mL in controls (p = 0.20). Log harmane concentrations were stratified based on the median value; 62% of cases vs 39% of controls had a high log harmane concentration (p = 0.001). Mean log harmane concentration was similar in the cases with (0.74 ± 0.58 g−10/mL) and without (0.71 ± 0.50 g−10/mL) an affected relative (p = 0.83). Conclusions: Blood concentrations of harmane were measured in ET cases compared with controls. Concentrations were elevated in cases with and without a family history of ET.

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.

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 Parkinsons 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 (β = 0.11; P = 0.02) and age (β = 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.

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 1H 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 |(value right − value left)|/(value right + value left) × 100. Multislice 1H 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.

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.

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.