Marina Gerbin

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.

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

Apathy, defined as decreased goal‐directed activity, has been observed in Parkinsons disease. A number of cognitive/psychiatric features have been documented in essential tremor, yet we are unaware of studies of apathy.

Depressive traits in essential tremor: impact on disability, quality of life, and medication adherence.

There is growing study of the psychiatric features of essential tremor. Depressive symptoms occur in a considerable number of patients. Yet their impact, as a primary factor, has received almost no attention. We assessed whether, independent of tremor severity, patients with more depressive symptoms have more perceived tremor‐related disability, lower tremor‐related quality of life, and poorer compliance with tremor medication.

Essential tremor 10, 20, 30, 40: clinical snapshots of the disease by decade of duration.

Essential tremor (ET) is a chronic, progressive neurological disorder in which disease burden may slowly accrue. There are few long‐term studies, and the clinical and functional status of patients, with each decade of disease duration, has not been documented in detail. We used cross‐sectional data on 335 patients with ET (disease duration 1–81 years) to produce clinical snapshots of the disease at each 10‐year milestone (i.e. < 10, 10–19, 20–29, 30–39, ≥ 40 years). We hope these data will be of value in clinical‐prognostic settings both to patients and their treating physicians.

Functional correlates of gait and balance difficulty in essential tremor: Balance confidence, near misses and falls

BACKGROUND Although a mild objective abnormality of gait and balance has been observed in essential tremor (ET) cases in research settings, the clinical significance of this finding for patients is far from clear. In this study, we assessed whether ET patients subjectively experience more gait difficulty, more falls or near misses than controls. METHODS Activities-specific Balance Confidence (ABC) scores were obtained in 59 ET cases (15 with head tremor and 44 without head tremor) and 82 controls enrolled in a clinical-epidemiological study. RESULTS ABC scores were lower in ET cases than controls (61.8 ± 27.7 vs. 70.3 ± 28.1, p=0.035) of similar age (71.2 ± 14.6 years vs. 71. 6 ± 0.8 years), indicating significantly lower balance confidence in cases. The lowest scores (51.4 ± 26.9) were observed in cases with head tremor (p=0.02). Near misses in the past year were the highest in cases with head tremor (67.3 ± 112.1) and lowest in controls (6.1 ± 33.3, p=0.008). The proportion who had had ≥ 5 near misses or falls in the past year was 11 (13.4%) for controls, 8 (18.2%) for cases without head tremor and 6 (40.0%) for cases with head tremor (p=0.048). For the ABC score, we created a receiver operating curve (ROC) curve and optimal cut-off score to differentiate between our two most different groups, namely, ET with head tremor and controls. Using this cut-off (≤ 67), sensitivity and specificity were moderate. CONCLUSIONS ET patients experience a loss of confidence in balance. The subgroup of patients with head tremor experienced the most gait and balance difficulty, with nearly one-in-two having had multiple near misses or falls during the previous year.

Development of an essential tremor embarrassment assessment.

INTRODUCTION Embarrassment is commonly reported in essential tremor (ET) patients yet there is no formal tool to assess embarrassment in ET. Our aim was to develop such a tool and to assess its clinimetric properties. A quantitative measure of embarrassment could be used to assess response to treatment in clinical practice and clinical trials. METHODS Based on surveys of international tremor experts and ET patients, we constructed the Essential Tremor Embarrassment Assessment (ETEA), a brief, easily administered, 14-item self-assessment scale. The ETEA was assessed for validity, reliability and other clinimetric properties in 75 ET patients. RESULTS Forty-seven tremor experts from eight countries were surveyed. On average, they estimated that 75% of their patients experienced embarrassment, yet there was very little agreement (range = 10-95%). Among ET patients, three-quarters (77.3%) reported at least occasional embarrassment due to their tremor and one-third (36.4%) reported daily embarrassment. ETEA scores correlated with a tremor disability questionnaire score (p = 0.02 and p = 0.01) and Center for Epidemiologic Studies Depression Scale scores (p<0.001 and p<0.001). Test-retest reliability was high (p<0.001). Factor analysis identified four factors, explaining 62.4% of the variance. For the major factors (I and II), high internal consistency was found (Cronbachs alpha = 0.85 and 0.74). CONCLUSION Embarrassment is commonly experienced by ET patients. The ETEA is a reliable and valid tool to measure embarrassment in patients with this disease.

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, blood lead, and severity of hand tremor: evidence of additive effects.

BACKGROUND Tremor is a widespread phenomenon in human populations. Environmental factors are likely to play an etiological role. Harmane (1-methyl-9H-pyrido[3,4-β]indole) is a potent tremor-producing β-carboline alkaloid. Lead is another tremor-producing neurotoxicant. The effects of harmane and lead with respect to tremor have been studied in isolation. OBJECTIVES We tested the hypothesis that tremor would be particularly severe among individuals who had high blood concentrations of both of these toxicants. METHODS Blood concentrations of harmane and lead were each quantified in 257 individuals (106 essential tremor cases and 151 controls) enrolled in an environmental epidemiological study. Total tremor score (range = 0-36) was a clinical measure of tremor severity. RESULTS The total tremor score ranged from 0 to 36, indicating that a full spectrum of tremor severities was captured in our sample. Blood harmane concentration correlated with total tremor score (p = 0.007), as did blood lead concentration (p = 0.045). The total tremor score was lowest in participants with both low blood harmane and lead concentrations (8.4 ± 8.2), intermediate in participants with high concentrations of either toxicant (10.5 ± 9.8), and highest in participants with high concentrations of both toxicants (13.7 ± 10.4) (p=0.01). CONCLUSIONS Blood harmane and lead concentrations separately correlated with total tremor scores. Participants with high blood concentrations of both toxicants had the highest tremor scores, suggesting an additive effect of these toxicants on tremor severity. Given the very high population prevalence of tremor disorders, identifying environmental determinants is important for primary disease prevention.

Voice Handicap in Essential Tremor: A Comparison with Normal Controls and Parkinson's Disease

Background Although voice tremor is one of the most commonly noted clinical features of essential tremor (ET), there are nearly no published data on the handicap associated with it. Methods The Voice Handicap Index (VHI) was self-administered by participants enrolled in a research study at Columbia University Medical Center. The VHI quantifies patients’ perceptions of handicap due to voice difficulties. Data from 98 ET cases were compared with data from 100 controls and 85 patients with another movement disorder (Parkinson’s disease, PD). Results Voice tremor was present on examination in 25 (25.5%) ET cases; 12 had mild voice tremor (ETMild VT) and 13 had marked voice tremor (ETMarked VT). VHI scores were higher in ET cases than controls (p = 0.02). VHI scores among ETMarked VT were similar to those of PD cases; both were significantly higher than controls (p<0.001). The three VHI subscale scores (physical, functional, emotional) were highest in ETMarked VT, with values that were similar to those observed in PD. Discussion The voice handicap associated with ET had multiple (i.e., physical, functional, and emotional) dimensions. Moreover, ET cases with marked voice tremor on examination had a level of self-reported voice handicap that was similar to that observed in patients with PD.