Intention Tremor of the Legs in Essential Tremor: Prevalence and Clinical Correlates.

OBJECTIVE: To estimate the prevalence and assess the clinical correlates of intention tremor in the legs in essential tremor (ET) patients. BACKGROUND: The cerebellar features of ET are of growing interest to clinical neurologists. Arm tremor has an intentional component in many ET patients. Intention tremor in the legs, however, has never been systematically evaluated. METHODS: One-hundred-twenty-eight ET patients were enrolled in a clinical-epidemiological study at Columbia University. A videotaped neurological examination included 10 toe-to-target movements with each foot. Videotapes were independently reviewed by two movement disorder neurologists who noted the presence vs. absence of intentional leg tremor. Two patients underwent quantitative computerized tremor analysis to study the physiological characteristics of the tremor. RESULTS: Thirty-five patients (27.3%) had intentional leg tremor; in 21, tremor was unilateral and in 14 it was bilateral. The 35 patients with intentional leg tremor did not differ from the remaining 93 patients in their clinical characteristics. Analyses comparing the 14 patients with bilateral intentional leg tremor to the 93 patients with no intentional leg tremor showed trends towards longer disease duration and more severe intentional arm tremor in the former. Tremor analysis showed a 3-fold increase in average tremor amplitude from movement onset to the point just prior to touching the target. CONCLUSIONS: Our data suggest that intentional leg tremor, another cerebellar feature, is common in ET patients. The tremor may be associated with longer disease duration and more severe intentional arm tremor, but these preliminary trends need to be assessed in larger study samples.

Non-steroidal anti-inflammatory drug use and essential tremor.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to be inversely related to Parkinson's disease and Alzheimer's disease, both of which may share common mechanisms with essential tremor (ET). Use of these medications has not been studied in ET cases vs. controls. OBJECTIVE: To investigate the relationships between NSAID (esp. ibuprofen) and aspirin use and ET. METHODS: Subjects were enrolled in a case-control study of the environmental epidemiology of ET at the Columbia University Medical Center (CUMC; 2009-2014). We compared 92 ET cases to 107 controls (∼1:1 matching) in terms of self-reported NSAID (esp. ibuprofen) and aspirin use. RESULTS: The proportion of NSAID or aspirin users (current or past) was similar in ET cases and controls (for current user, p = 0.66; for past user, p = 0.90). Among users, however, the total dosage of ibuprofen (frequency in past year × number of tablets taken at a time × typical average strength of tablets) was higher in controls than ET cases (p = 0.04). ET cases and controls did not differ with respect to aspirin use in the past year. CONCLUSION: The proportion of NSAID or aspirin users did not differ in ET cases or controls; yet interestingly, ibuprofen use was less in ET cases than in controls. The latter raises the possibility that ibuprofen use could have a potential protective role in ET.

Incidence rates of cranial tremors in essential tremor: a prospective, longitudinal study.

BACKGROUND: Cranial (head, jaw) tremors develop in a sizable number of essential tremor (ET) patients. They are particularly important because they are a significant source of embarrassment and are especially resistant to treatment. There are no data on the rate at which ET patients develop these cranial tremors. Our aim was to estimate the incidence rate of head and jaw tremors in ET. METHODS: Cases, enrolled in a prospective, longitudinal study, were evaluated at baseline and one follow-up visit. The in-person evaluation included questionnaires and a videotaped neurological examination, which was reviewed by a senior movement disorder neurologist for the presence/absence of head and jaw tremors. The mean time between baseline and follow-up assessments was 6.3 ± 2.4 (median = 6.0; range = 1.5-12.4 years). RESULTS: Five (6.3%) of 79 cases developed head tremor by follow-up (incidence rate = 1,012 per 100,000 person years; 95% confidence interval [CI] = 0-3,219). Twelve (10.6%) of 113 cases developed jaw tremor by follow-up (incidence rate = 1,692 per 100,000 person years; 95% CI = 0-1,692). CONCLUSION: These epidemiological data were designed to assist physicians in counseling ET patients when they ask about their risks of developing cranial tremors.

Validity of a screening question for head tremor: an analysis of four essential tremor case samples.

BACKGROUND: The goal of this study was to assess the validity of a screening question for head tremor in essential tremor (ET). There are no published data on this topic, and the knowledge will guide future epidemiological investigations of this disorder. METHODS: These analyses utilized four distinct patient samples: a population-based study in northern Manhattan, a study of the environmental epidemiology of ET, a genetics study, and a brain repository. Sensitivity was the proportion of ET cases with head tremor on examination who self-reported head tremor. RESULTS: The sensitivity of the screening question for head tremor was lowest in the population-based study (31.6%), and higher as well as somewhat similar across the remaining studies (46.7 to 62.2%). Higher sensitivity was associated with tremor of longer duration, presence of voice tremor on examination, female gender, and lower education. The use of the screening question would have increased case ascertainment during the screening phase of these four studies by 1.9, 4.1, 10.2, and 20.3%. CONCLUSIONS: A screening question for head tremor had low-to-moderate sensitivity in ET. The use of such a screening questionnaire, however, has the potential to increase case ascertainment by as much as 20% in some screening settings.

Semi-quantitative data on ethanol consumption in 354 ET cases and 370 controls.

The notion that there is an association between essential tremor (ET) and higher ethanol consumption has crept into the literature; however, the data are limited and conflicted. A total of 354 ET cases and 370 matched controls were enrolled in a clinical-epidemiological study. Average current daily ethanol consumption was estimated using the Willett Semi-quantitative Food Frequency Questionnaire. The proportion of cases and controls who drank any ethanol was similar: 66.7% vs. 64.1%, p=0.46, as was the proportion who reported heavy ethanol consumption: 4.0% vs. 3.5%, p=0.74. The average daily ethanol intake was numerically higher in cases than controls (7.99 ± 12.39 [median=3.03] vs. 6.55 ± 10.62 [median=1.80] g), but this difference did not reach significance (p=0.15). Among cases, there was no correlation between average daily ethanol intake and tremor severity (r=0.008, p=0.88). These data, on more than 700 enrollees, do not support any sizable differences between ET cases and controls in terms of average daily ethanol consumption or ethanol overuse. The absence of a correlation in cases between ethanol consumption and tremor severity goes against the hypothesis that ET patients are self-medicating to a significant degree.

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in dystonia cases vs. controls.

BACKGROUND: Harmane (1-methyl-9H-pyrido[3,4-b]indole) (HA) is a potent neurotoxin that has been linked to two neurological diseases, essential tremor and Parkinson's disease. Blood harmane concentrations [HA] are elevated in patients with both diseases. An important question is whether HA is specifically linked with these diseases or alternatively, is a non-specific marker of neurological illness. OBJECTIVES: We assessed whether blood [HA] was elevated in patients with a third neurological disease, dystonia, comparing them to controls. METHODS: Blood [HA] was quantified by high performance liquid chromatography. Subjects comprised 104 dystonia cases and 107 controls. RESULTS: Mean log blood [HA] in dystonia cases was similar to that of controls (0.41±0.51g(-10)/ml vs. 0.38±0.61g(-10)/ml, t=0.42, p=0.68). In unadjusted and adjusted logistic regression analyses, log blood [HA] was not associated with the outcome (diagnosis of dystonia vs. control): odds ratio (OR)unadjusted=1.11, 95% confidence interval (CI)=0.69-1.79, p=0.68; ORadjusted=1.07, 95% CI=0.58-1.97, p=0.84. CONCLUSIONS: In contrast to the elevated blood [HA] that has been reported in patients with essential tremor and Parkinson's disease, our data demonstrate that blood [HA] was similar in patients with dystonia and controls. These findings provide the first support for the notion that an elevated blood [HA] is not a broad feature of neurological disease, and may be a specific feature of certain tremor disorders.

The spiral axis as a clinical tool to distinguish essential tremor from dystonia cases.

BACKGROUND: Tremor is a common feature of a variety of neurological disorders. In genetic studies of essential tremor (ET), investigators need to screen potential enrollees by mail or telephone to exclude those with other neurological conditions, especially dystonia. In clinical settings, the differentiation of ET and dystonia may also be very challenging. We hypothesized that the spiral axis, described below, is a useful screening tool to distinguish ET cases from dystonia cases. METHODS: We analyzed the hand-drawn spirals of 135 individuals enrolled in a genetics study at Columbia University Medical Center. Each of the four spirals was assessed for the presence of a single identifiable tremor orientation axis, and a spiral axis score (range = 0-4) [a single axis on all 4 spirals] was assigned to each enrollee. RESULTS: There were 120 ET cases and 15 cases with dystonic tremor. Most (101/120, 84.2%) ET cases had an axis score ≥1 vs. only half (8/15, 53.3%) of the dystonia cases (p = 0.02). Receiver Operator Curve (ROC) analysis revealed that the use of a spiral axis score ≥2 as a cut off would exclude 60.0% of dystonia cases while including 67.5% of ET cases. CONCLUSION: Handwritten spirals appear to have a single predominant axis in more ET than dystonia cases. The evaluation of this axis has moderate diagnostic validity as a screening tool to distinguish ET cases from those with dystonia. Although this study did not assess the utility of this tool in clinical practice settings, future studies should do so.

Triggering essential head tremor with sustained phonation: a clinical phenomenon with potential diagnostic value.

Here we report a clinical phenomenon that we have observed repeatedly in clinical research settings; namely, a triggering and/or exacerbation of head tremor during or immediately following sustained phonation. To our knowledge, it has not been reported previously nor has it been the subject of study. Here we: 1) report the phenomenon, 2) provide several visual illustrations, 3) estimate its prevalence, and 4) analyze its clinical correlates. Head tremor was assessed qualitatively, and scores were assigned pre-, during, and post-sustained phonation using the Tremor Research Group Essential Tremor Rating Assessment Scale. Seventy (68.6%) of 102 essential tremor (ET) patients exhibited a qualitative increase in head tremor amplitude during and/or immediately after sustained phonation; in 5 (4.9%), head tremor would not have been detected without the voice activation maneuver (i.e., it was not visible at any other point in the videotape aside from the period during/immediately following sustained phonation). Women were more likely than men to exhibit this phenomenon (p = 0.05), whereas age, age at onset, duration of tremor, and total tremor score did not predict responsiveness of head tremor to sustained phonation. Sustained voice activation is a useful examination maneuver that may elicit or amplify head tremor in ET. Head tremor is not reported to occur in patients with enhanced physiological tremor. Thus, this maneuver, by triggering head tremor, may be a useful diagnostic supplement, particularly in research/clinical settings where arm tremor is mild and the diagnosis (mild ET vs. enhanced physiological tremor) would otherwise be ambiguous.

Elevated blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a late-life neurodegenerative disease. Genetic and environmental factors play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin that shows structural resemblance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). OBJECTIVES: In 2002 and 2007, we demonstrated elevated blood harmane concentrations [HA] in essential tremor (ET) cases. We now assessed whether blood [HA] were elevated in Parkinson's disease (PD) as well. METHODS: Blood [HA] were quantified by high performance liquid chromatography. Subjects comprised 113 PD cases and 101 controls. RESULTS: Mean log blood [HA] in PD cases was double that of controls (0.59±0.63 g(-10)/ml vs. 0.27±0.63 g(-10)/ml, p<0.001). A non-parametric test on non-transformed data (median blood [HA]=3.31 g(-10)/ml in cases and 1.44 g(-10)/ml in controls) also showed this difference (p<0.001). In unadjusted and then adjusted logistic regression analyses, log blood [HA] was associated with PD (odds ratio [OR]unadjusted 2.31, 95% confidence interval [CI] 1.46-3.67, p<0.001; OR(adjusted) 2.54, 95% CI 1.55-4.16, p<0.001). In PD, log blood [HA] co-varied with family history, being lowest in PD cases with no family history (0.54±0.60 g(-10)/ml) and highest in PD cases with a family history of both ET and PD (0.84±0.68 g(-10)/ml) (p=0.06). CONCLUSIONS: Blood harmane appears to be elevated in PD. The finding needs to be reproduced in additional cohorts to assess its generalizability. The higher concentration in familial PD suggests that the mechanism may involve genetic factors.