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Background: Essential tremor (ET) is a highly prevalent neurological disease that frequently runs in families. A recent and controversial proposal is to separate ET patients into two distinct groups – ET vs. ET-plus. If this were a valid construct, one would expect in familial aggregation studies to observe that ET-plus would cluster in some families yet be absent in others, rather than being randomly distributed across families. We examined whether there is evidence of familial aggregation of ET-plus. Methods: Probands (n=84 [56 ET-plus and 28 ET]) and their first- and second-degree relatives (n=182 and 48) enrolled in a genetics study. Chi-squares and generalized estimating equations (GEE) tested associations between probands’ ET-plus status and the ET-plus status of their relatives. Results: Chi-squares analyses revealed that ET-plus was no more prevalent in relatives of probands diagnosed with ET-plus than in relatives of probands diagnosed with ET, p>0.05. Restricting relatives to first-degree relatives similarly did not detect a significant association (p = 0.88). GEE yielded similar results (respective p’s = 0.39 and 0.81). Conclusion: The data demonstrate that ET-plus does not seem to aggregate in families. As such, they do not lend support to the notion that ET-plus is a valid biological construct.

BackgroundFew longitudinal studies assess the progression of essential tremor (ET). One unexplored issue is whether tremor severity increases across time at a uniform rate. That is, does the observed rate of change in tremor severity within a particular patient remain constant or vary across time? This question of intra-individual differences is particularly important since it reflects a primary patient concern–will the nature of change I have seen to date be what I can expect in the future?MethodsET cases were enrolled in a prospective, longitudinal study. We selected 35 cases and assessed tremor severity via Bain and Findley ratings of Archimedes spirals assigned by a senior movement disorders neurologist. After reviewing both the change in spiral scores and the rate of change in scores, we identified five mutually exclusive patterns of severity change. We calculated the prevalence of each category using two complementary sets of classification criteria.ResultsLength of follow-up was 4.5 to 16.0 years, mean=10.2 years. Mean baseline tremor severity score was 4.6, SD=1.6. Depending upon the classification criteria used, the tremor scores of one-third to one-half of cases did not increase in a uniform fashion but were better described as demonstrating jumps and/or reversals in scores across time.ConclusionsWe document the nature of changes in ET tremor severity scores across a ten-year period via expert ratings of Archimedes spiral drawings. Such natural history data are valuable to patients and clinicians who hope to better understand and predict the likely course of ET symptoms.

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Brain donation is a challenging process, comprising four sequential stages: (1) the brain donation decision, (2) pre-mortem arrangements and follow up, (3) specimen collection and (4) tissue processing. It is important to understand the factors that are pertinent to each stage. Currently, there is extensive information on factors that involve donor's personal and cultural backgrounds and how these could affect the process. However, little is known about disease-specific factors that influence the process. The Essential Tremor Centralized Brain Repository was established in 2003, and after nearly 20 years of collecting essential tremor (ET) brain tissue, we are well-positioned to discuss the brain donation process from a disease-specific standpoint. In the current manuscript, we discuss ET disease-specific factors that influence the first two stages of the brain donation process. We center our discussion around three points: (1) factors that influence the patient's decision to donate, (2) the involvement of next of kin in the donation, and (3) the rationale for enrolling patients prospectively and evaluating them longitudinally before the anatomical gift takes place. This discussion shares our understanding of the background from which our repository operates and may be of value for other brain banks that study similar neurodegenerative diseases.

BackgroundPeople with essential tremor (ET) can be subject to stigma, and some adopt avoidance behaviors. Characteristics associated with ET stigma and the relationship between perceived stigma and social dysfunction have not been studied.ObjectivesTo discern predictors of perceived stigma and social dysfunction in ET, and to identify potentially treatable psychological factors associated with social dysfunction.MethodsWe surveyed ET patients (n = 158) on recalled stigma incidents and social dysfunction related to tremor, as well as clinical and demographic characteristics including tremor severity, and psychological constructs including anxiety, depression, mindfulness, resilience, and narcissism.ResultsWorse tremor severity (Standardized beta [SB] 1.4, P < 0.001) especially among younger participants (interaction of age and tremor severity SB −0.9, P < 0.001) and presence of vocal tremor (SB 0.7, P = 0.002) predict perceived stigma. 53/157 (33.8%) participants met criteria for social dysfunction, employing maladaptive avoidance strategies. Scores for perceived stigma (Odds Ratio [OR] 1.2, P = 0.002), depression (OR 1.5, P = 0.004) and stigma psychological distress (OR 1.2, P = 0.001) as well as sex (OR 4.3 for females, P = 0.045) predicted social dysfunction.ConclusionsDepression and stigma psychological distress contribute to social dysfunction related to ET stigma. Treating these psychological factors may mitigate social avoidance behaviors prevalent among susceptible individuals: those who most perceive ET stigma, i.e. relatively younger patients with worse tremor or with vocal tremor, and in particular females who are more prone to social dysfunction than males with the same degree of perceived stigma.

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Background and ObjectivesThere has been a long-standing dialog as to whether essential tremor (ET) increases the risk of developing Parkinson disease (PD). While there are relevant cross-sectional data, there are almost no longitudinal prospective data. We quantified the conversion rate from ET to ETPD in a prospective longitudinal cohort study of patients with ET. We compared the observed rate with that reported in the epidemiologic literature.MethodsWe enrolled patients with ET in a prospective, longitudinal study. A senior movement disorders neurologist evaluated standardized neurologic examinations every 18 months.ResultsOne hundred ninety-three patients with ET (mean age = 78.1 ± 9.6 years, range = 55–96) had a mean follow-up duration of 4.1 years. Seven (3.6%) converted from ET to ETPD. The incidence of PD among patients with ET was 7/792.9 person-years (py; i.e., 882.8/100,000 py). A meta-analysis of the incidence (per 100,000 py) of PD in 14 studies from 13 countries across 4 continents reported an incidence of PD = 61.21 (men, 40 years or older) and 37.55 (women, 40 years or older). The incidence/100,000 py in men peaked in the 80- to 89-year-old age group (258.47) and in women in the 80- to 89-year-old age group (103.48 py). The abovementioned published values are 3.4–23.5 times lower than the value we observed for ET.DiscussionThe incidence of PD in an ET cohort is substantially higher than that reported in historical population-based control groups across numerous countries. Additional prospective longitudinal data are needed to further explore this association.