Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentration in essential tremor cases in Spain.

BACKGROUND: Environmental correlates for essential tremor (ET) are largely unexplored. The search for such environmental factors has involved the study of a number of neurotoxins. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing toxin. In two prior case-control studies in New York, we demonstrated that blood harmane concentration was elevated in ET patients vs. controls, and especially in familial ET cases. These findings, however, have been derived from a study of cases ascertained through a single tertiary referral center in New York. OBJECTIVE: Our objective was to determine whether blood harmane concentrations are elevated in familial and sporadic ET cases, ascertained from central Spain, compared to controls without ET. METHODS: Blood harmane concentrations were quantified by a well-established high performance liquid chromatography method. RESULTS: The median harmane concentrations were: 2.09 g(-10)/ml (138 controls), 2.41 g(-10)/ml (68 sporadic ET), and 2.90 g(-10)/ml (62 familial ET). In an unadjusted logistic regression analysis, log blood harmane concentration was not significantly associated with diagnosis (familial ET vs. control): odds ratio=1.56, p=0.26. In a logistic regression analysis that adjusted for evaluation start time, which was an important confounding variable, the odds ratio increased to 2.35, p=0.049. CONCLUSIONS: Blood harmane levels were slightly elevated in a group of familial ET cases compared to a group of controls in Spain. These data seem to further extend our observations from New York to a second cohort of ET cases in Spain. This neurotoxin continues to be a source of interest for future confirmatory research.

Blood harmane (1-methyl-9H-pyrido[3,4-b]indole) concentrations in essential tremor: repeat observation in cases and controls in New York.

Essential tremor (ET) is a widespread late-life neurological disease. Genetic and environmental factors are likely to play important etiological roles. Harmane (1-methyl-9H-pyrido[3,4-b]indole) is a potent tremor-producing neurotoxin. Previously, elevated blood harmane concentrations were demonstrated in ET cases compared to controls, but these observations have all been cross-sectional, assessing each subject at only one time point. Thus, no one has ever repeat-assayed blood harmane in the same subjects twice. Whether the observed case-control difference persists at a second time point, years later, is unknown. The current goal was to reassess a sample of our ET cases and controls to determine whether blood harmane concentration remained elevated in ET at a second time point. Blood harmane concentrations were quantified by a well-established high-performance liquid chromatography method in 63 ET cases and 70 controls. A mean of approximately 6 yr elapsed between the initial and this subsequent blood harmane determination. The mean log blood harmane concentration was significantly higher in cases than controls (0.30 ± 0.61 g(-10)/ml versus 0.08 ± 0.55 g(-10)/ml), and the median value in cases was double that of controls: 0.22 g(-10)/ml versus 0.11 g(-10)/ml. The log blood harmane concentration was highest in cases with a family history of ET. Blood harmane concentration was elevated in ET cases compared to controls when reassessed at a second time point several years later, indicating what seems to be a stable association between this environmental toxin and ET.

Mental Status Test Scores are Inversely Correlated with Tremor Severity: A Study of 161 Elderly Essential Tremor Cases.

BACKGROUND: There is an increasing awareness that patients with essential tremor (ET) may exhibit non-motor features, including cognitive dysfunction. Yet there are surprisingly few data in ET on the association, if any, between cognitive dysfunction and motor dysfunction (i.e., tremor severity). Establishing links between the cognitive and motor features of ET would imply that the two share a common underlying pathogenic process. Recent neuroimaging data support this notion. METHODS: ET cases were enrolled in a clinical-pathological study at Columbia University Medical Center, New York. The Folstein Mini-Mental State Examination (FMMSE) and Modified Mini Mental Status Examination (mMMSE) were administered. Action tremor was rated with a total tremor score (TTS). RESULTS: There were 161 ET cases (mean age 83.9±5.7 years, median FMMSE 28, median mMMSE 50). The FMMSE and mMMSE were inversely correlated with the TTS (r = -0.22, p = 0.005; and r = -0.17, p = 0.029). The association, while statistically significant, was modest in magnitude. In linear regression models that adjusted for age, gender, and education, the association between cognitive test scores and TTS remained robust (p<0.001). After excluding 68 (42.2%) cases taking ET medications with potential cognitive side effects, results remained unchanged. CONCLUSIONS: Each of the two cognitive test scores was associated with tremor severity such that greater cognitive dysfunction occurred in cases with more marked tremor. These data support recent imaging data, which suggest that the cerebellar neurodegeneration underlying ET may be involved in the expression of cognitive symptoms in ET.

Sleep in essential tremor: a comparison with normal controls and Parkinson's disease patients.

BACKGROUND: Recent studies have shed light on non-motor features of ET, such as depressive symptoms and cognitive changes, which might be attributed to pathophysiological changes in the brains of ET patients. Given these brain changes, we explored sleep abnormalities in ET patients. METHODS: Sleep was assessed using the Epworth Sleepiness Scale (ESS) and the Pittsburgh Sleep Quality Index (PSQI) in 120 ET cases, 120 normal controls, and 40 PD cases. RESULTS: The mean±SD (median) ESS score increased from normal controls (5.7±3.7 (5.0)), to ET cases (6.8±4.6 (6.0)), to PD cases (7.8±4.9 (7.0)), test for trend p=0.03. An ESS score >10 (an indicator of greater than normal levels of daytime sleepiness) was observed in 11 (9.2%) normal controls, compared to 27 (22.5%) ET cases and 10 (25.0%) PD cases (p=0.008 when comparing all three groups, and p=0.005 when comparing ET to normal controls). The global PSQI score was 7.8±2.8 (7.5) in controls, 8.0±3.3 (8.0) in ET cases, and 9.9±3.9 (10.0) in PD cases. The ET case-control difference was not significant (p=0.8), yet in a test for trend, PD cases had the highest PSQI score (most daytime sleepiness), followed by ET (intermediate), and lowest scores in controls (p=0.02). CONCLUSIONS: Some sleep scores in ET were intermediate between those of PD cases and normal controls, suggesting that a mild form of sleep dysregulation could be present in ET.

Apathy in essential tremor, dystonia, and Parkinson's disease: a comparison with normal controls.

BACKGROUND: Apathy, defined as decreased goal-directed activity, has been observed in Parkinson's disease. A number of cognitive/psychiatric features have been documented in essential tremor, yet we are unaware of studies of apathy. METHODS: Using the Apathy Evaluation Scale (range = 18-72 [more apathy]), we compared 79 essential tremor cases, 20 dystonia cases, and 39 Parkinson's disease cases with 80 normal controls. RESULTS: The score of the Apathy Evaluation Scale was higher in essential tremor, dystonia, and Parkinson's disease cases than controls (all P ≤ .04). Parkinson's disease cases had the highest scores. Analyses stratified by presence/absence of depressive symptoms indicated the presence of a group of apathetic but nondepressed cases. CONCLUSIONS: Patients with Parkinson's disease, essential tremor, and dystonia had elevated apathy scores. Features of apathy seemed to occur in these conditions independent of depressive symptoms. The mechanistic basis for the apparent increased features of apathy in essential tremor and dystonia deserves further study.

Estimating annual rate of decline: prospective, longitudinal data on arm tremor severity in two groups of essential tremor cases.

BACKGROUND: Despite its high prevalence, there are surprisingly few prospective, longitudinal data on the clinical course of essential tremor (ET). Patients themselves often want to know from their treating physician whether and by how much their tremor is expected to worsen over time. METHODS: As part of two research protocols, prospective, longitudinal data were collected on tremor severity in two samples of ET cases (44+39 cases, combined n=83). At a baseline and one follow-up evaluation, a detailed clinical assessment was performed and action tremor in the arms was rated by a senior movement disorders neurologist using a standardised clinical rating scale (Total Tremor Score (TTS), range 0-36). RESULTS: In the first case sample, TTS increased annually by 0.32 ± 0.89 points (ie, an annual increase of 5.3 ± 17.1% (median 1.8%) from the mean baseline score). TTS increased by ≥ 0.5 points in 23/24 (95.8%) cases followed for ≥ 5 years. In the second sample, TTS score increased annually by 0.64 ± 1.49 points (annual increase of 3.1 ± 8.1% (median 2.0%) from the mean baseline score). TTS increased by ≥ 0.5 points in 11/15 (73.3%) cases followed for ≥ 5 years. No baseline factors were identified that predicted annual change in TTS. CONCLUSIONS: Most ET cases exhibited a progressive worsening in tremor scores with time such that the average annual increase in tremor severity from baseline was estimated to be between 3.1% and 5.3% and the median annual increase from baseline was between 1.8% and 2.0%. These published estimates will hopefully be a useful prognostic guide for clinicians and their patients.