LaKeisha M. Applegate

Blood harmane concentrations and dietary protein consumption in essential tremor

Background: β-Carboline alkaloids (e.g., harmane) are highly tremorogenic chemicals. Animal protein (meat) is the major dietary source of these alkaloids. The authors previously demonstrated that blood harmane concentrations were elevated in patients with essential tremor (ET) vs controls. Whether this difference is due to greater animal protein consumption by patients or their failure to metabolize harmane is unknown. Objective: The aim of this study was to determine whether patients with ET and controls differ with regard to 1) daily animal protein consumption and 2) the correlation between animal protein consumption and blood harmane concentration. Methods: Data on current diet were collected with a semiquantitative food frequency questionnaire and daily calories and consumption of animal protein and other food types was calculated. Blood harmane concentrations were log-transformed (logHA). Results: The mean logHA was higher in 106 patients than 161 controls (0.61 ± 0.67 vs 0.43 ± 0.72 g−10/mL, p = 0.035). Patients and controls consumed similar amounts of animal protein (50.2 ± 19.6 vs 49.4 ± 19.1 g/day, p = 0.74) and other food types (animal fat, carbohydrates, vegetable fat) and had similar caloric intakes. In controls, logHA was correlated with daily consumption of animal protein (r = 0.24, p = 0.003); in patients, there was no such correlation (r = −0.003, p = 0.98). Conclusions: The similarity between patients and controls in daily animal protein consumption and the absence of the normal correlation between daily animal protein consumption and logHA in patients suggests that another factor (e.g., a metabolic defect) may be increasing blood harmane concentration in patients.

Interaction between blood lead concentration and δ-amino-levulinic acid dehydratase gene polymorphisms increases the odds of essential tremor

Blood lead (BPb) concentrations are elevated in essential tremor (ET) cases. The δ‐amino‐levulinic acid dehydratase (ALAD) gene codes for ALAD, the principal enzyme involved in lead kinetics. Carriers of the ALAD‐2 allele may be more susceptible to lead toxicity. The objective of this study was to test, using a case‐control design, whether an interaction between BPb concentration and ALAD allele status increases the odds of ET. Mean log BPb concentration was significantly higher in 63 cases than 101 controls (0.47 ± 0.26 vs. 0.35 ± 0.25 μg/dl). Eighteen (28.6%) cases vs. 17 (16.8%) controls had an ALAD‐2 allele (OR = 1.98; 95% CI = 0.93–4.21). In an adjusted logistic regression analysis, the interaction term (ALAD allele status × log BPb concentration) was associated with increased odds for ET. In stratified analyses, log BPb concentration was not associated with odds of ET in individuals with two ALAD‐1 alleles (OR = 2.69; 95% CI = 0.61–11.82), but in individuals with an ALAD‐2 allele, BPb concentration was significantly associated with odds of ET (OR = 80.29; 95% CI = 3.08–2,096.36). There was an interaction between BPb concentration and ALAD allele status; the odds of ET were greatly elevated in individuals with both an ALAD‐2 allele and an elevated BPb concentration. The presence of increased circulating BPb concentrations along with a greater potential for lead toxicity (ALAD‐2 allele) could result in greater cerebellar damage, thereby increasing the risk of developing tremor.

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 Parkinsons disease (PD), raises the question whether jaw tremor in ET is a marker for subsequent conversion to PD.

Essential tremor Occupational exposures to manganese and organic solvents

Occupational exposures to manganese and organic solvents cause parkinsonism as well as prominent action tremor, resembling essential tremor (ET), yet their association with ET has not been studied. These chemicals cause cerebellar pathology. Cerebellar changes have been linked with ET. Using lifetime occupational histories, the authors demonstrated that occupational exposures were similar in cases and controls, which does not support an etiologic link between occupational exposures to these chemicals and 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.

ICD-9 CM Code 333.1 as an Identifier of Patients with Essential Tremor: A Study of the Positive Predictive Value of This Code

Background/Aims: Health outcomes research often uses administrative databases. Patients with the diseases of interest are identified using International Classification of Diseases (ICD-9 CM) codes. The utility of the code for essential tremor (ET), 333.1, remains untested. We determined the positive predictive value (PPV) of the code 333.1. Methods: Patients with the ICD-9 CM code 333.1 were identified from billing records at the Neurological Institute of New York. Their medical records were reviewed to determine whether they met Consensus Criteria for ET. Results: Of 964 patients who carried the code 333.1, only 472 met diagnostic criteria for ET (i.e. PPV = 49.0%). The additional use of ICD 9-CM codes for parkinsonism and dystonia (as exclusionary criteria) only marginally improved this value (57.8%). Common diagnoses among the false positives were Parkinson’s disease, dystonia, enhanced physiological tremor, drug-induced tremor, orthostatic tremor, and psychogenic tremor. Patients seen by general neurologists (vs. movement disorder specialists) were half as likely to meet diagnostic criteria for ET (34.6 vs. 51.9%, OR 0.50, 95% CI 0.23–0.70, p < 0.001). Conclusion: The code 333.1 performed poorly when attempting to identify ET cases. Given the very high prevalence of ET, a unique diagnostic code would seem to be in order.

Factor Structure of Motor Signs in Essential Tremor

Motor signs in essential tremor (ET) are varied. Patients may have limb tremors, including postural, kinetic (e.g. writing, pouring), and rest tremors, head tremor, voice tremor, or chin tremor. Factor analysis allows one to determine whether these signs fall into a smaller number of discrete domains. Such an analysis has not been performed on a group of ET cases. ET cases (n = 168) were recruited from the Neurological Institute of New York and a videotaped examination was performed. A factor analysis was performed on 17 motor items. Four distinct factors emerged, explaining 68.7% of the total variance. These were factor I (action tremor in the dominant arm), factor II (action tremor in the nondominant arm), factor III (tremor at rest) and factor IV (chin tremor, head tremor, and voice tremor). The demonstration of these four factors will be of potential use for pathological and genetic studies as well as interventional studies, as will be discussed.

Feasibility and validity of a modified finger-nose-finger test

In essential tremor (ET) research, it is important to obtain standardized, objective data on tremor severity. Often, it is not possible to carry out in‐person or videotaped neurological examinations. In place of these, handwriting samples can be collected, but they do not capture all of the variance in tremor severity. Although additional tests of tremor severity (finger‐nose‐finger [FNF] test) might be of use, these would need to be modified to allow ET patients to mail their results to the study investigator for rating. We modified the standard FNF test (sFNF) by asking subjects to hold a pen during this activity and mark a paper target. The purpose of this report was to determine whether the modified FNF (mFNF) test was feasible and valid. Of 70 subjects, 65 (92.9%) were able to complete the mFNF, demonstrating that it was feasible. The scores of the mFNF correlated highly with those of the sFNF (r = 0.56–0.85; all P < 0.001), indicating the mFNF is a valid measure of tremor severity. In addition, using the regression equation, sFNF = 0.174(mFNF) + 0.743, a sFNF score can be derived easily from the mFNF score. The mFNF may be used to collect valuable data on tremor severity in pathological, genetic, and epidemiological field studies of ET, in which in‐person or videotaped neurological examinations are not possible.

Declaration of San Antonio, Texas

• Despite the fact that vascular dementia is the second-most common form of dementia in the elderly after Alzheimer’s disease, very few trials are being conducted on the use of existing and developing therapies for this devastating condition. Therefore, it is the hope of the members of this international scientific society that Governments around the world, scientific funding agencies, and the pharmaceutical industry will recognize the importance of this problem and implement Public Health and research programs for the prevention and treatment of the deleterious consequences of vascular injury to the brain.

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.