Essential Tremor Cases Research Articles

Baseline Depressive Symptoms as a Predictor of Incident Dementia in a Prospectively Followed Cohort of Elders with Essential Tremor

Introduction: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. Methods: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants’ baseline depression scores. Results: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02–1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02–1.25, p = 0.02). Conclusion: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population.

Subjective Sleep Disturbance and Lewy Pathology: Data from a Cohort of Essential Tremor Brain Donors

Introduction: Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases. Methods: Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last – first), and LP on postmortem brain examination. Results: ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last – first sleep latency component score) was associated with presence of LP on postmortem brain examination – greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04). Conclusion: In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.

GWAS meta-analysis reveals key risk loci in essential tremor pathogenesis

Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson’s disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.

Pathologically based criteria to distinguish essential tremor from controls: analyses of the human cerebellum.

Essential tremor is among the most prevalent neurological diseases. Diagnosis is based entirely on neurological evaluation. Historically, there were few postmortem brain studies, hindering attempts to develop pathologically based criteria to distinguish essential tremor from control brains. However, an intensive effort to bank essential tremor brains over recent years has resulted in postmortem studies involving >200 brains, which have identified numerous degenerative changes in the essential tremor cerebellar cortex. Although essential tremor and controls have been compared with respect to individual metrics of pathology, there has been no overarching analysis to derive a combination of metrics to distinguish essential tremor from controls. We asked whether there is a constellation of pathological findings that separates essential tremor from controls, and how well that constellation performs. Analyses included 100 essential tremor brains from the essential tremor centralized brain repository and 50 control brains. A standard tissue block from the cerebellar cortex was used to quantify 11 metrics of pathological change. Three supervised classification algorithms were investigated, with data divided into training and validation samples. Using three different algorithms, we illustrate the ability to correctly predict a diagnosis of essential tremor, with sensitivity and specificity >87%, and in the majority of situations, >90%. We also provide a web-based application that uses these metric values, and based on specified cutoffs, determines the likely diagnosis. These analyses set the stage for use of pathologically based criteria to distinguish clinically diagnosed essential tremor cases from controls, at the time of postmortem.

Evaluation of Hearing Loss in Patients with Essential Tremor

ABSTRACT Background: Essential tremor (ET) is a common chronic progressive disease, characterized by postural and action tremor. Abnormalities within the cerebello-thalamocortical pathways are thought to be involved in ET. In some studies, it was reported that there is an association between ET and hearing loss. Objective: In this study, our goal is to examine the electrophysiological changes of the structures forming the auditory pathway in ET cases, and the relationship of these changes with clinical findings and understand if the pathology underlying hearing loss in ET is cochlear or retrocochlear. Materials and Methods: One hundred sequential ET patients who had referred to Mersin University Faculty of Medicine Neurology Department, and 100 healthy individuals that are equivalent in terms of age and gender were conducted to investigate this association. Detailed medical history, neurologic examination, audiologic examination, pure-tone audiometry (PTA), tympanometry, and auditory brainstem response (ABR) analyses also known as brainstem auditory-evoked potentials were applied to all patients and controls. Results: The mean age of patients with ET was 56.38 ± 16.73, and the mean age of individuals in the control group was 56.47 ± 16.86. Nineteen of the patients with ET, and two healthy individuals from the control group had hearing problems (P < 0.001). In this study, there were no significant differences found in audiometric and ABR examinations in terms of hearing loss between the ET group and control group. However, in audiometric and ABR analyses, an increase in hearing loss was found to be correlated with an increase in tremor severity. In PTA test, hearing loss was higher in those with high-intensity tremor severity than in the group with mild tremor severity. This was statistically significant. P (KW) <0.05 Pposthoc < 0.05. In ABR analysis, it was found that there was a statistically significant difference with the increase of tremor severity at the dominant hand with: wave V latencies of the right and left ear; I-V interpeak latencies of the right ear, and III-V interpeak latencies of the right ear. The difference was between mild and moderate tremor groups. Conclusion: This study shows that there could be an impairment in inhibiting the functional transmission in the brainstem of patients with ET.

Disparities in the treatment of movement disorders using deep brain stimulation.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) and essential tremor (ET). Although the prevalence of PD and ET can vary by sex and race, little is known about the accessibility of neurosurgical treatments for these conditions. In this nationwide study, the authors aimed to characterize trends in the use of DBS for the treatment of PD and ET and to identify disparities in the neurosurgical treatment of these diseases based on ethnic, racial, sex, insurance, income, hospital, and geographic factors. Using the dates January 1, 2012, to December 31, 2019, the authors queried the National Inpatient Sample database for all discharges with an ICD-9 or ICD-10 diagnosis of PD or ET. Among these discharges, the DBS rates were reported for each subgroup of race, ethnicity, and sex. To develop national estimates, all analyses were weighted. Among 2,517,639 discharges with PD, 29,820 (1.2%) received DBS, and among 652,935 discharges with ET, 11,885 (1.8%) received DBS. Amid the PD cases, Black patients (n = 405 [0.2%], OR 0.16, 95% CI 0.12-0.20) were less likely than White patients (n = 23,975 [1.2%]) to receive DBS treatment, as were Hispanic patients (n = 1965 [1.1%], OR 0.76, 95% CI 0.65-0.88), whereas Asian/Pacific Islander patients (n = 855 [1.5%]) did not statistically differ from White patients. Amid the ET cases, Black (n = 230 [0.8%], OR 0.39, 95% CI 0.27-0.56), Hispanic (n = 215 [1.0%], OR 0.39, 95% CI 0.28-0.55), and Asian/Pacific Islander (n = 55 [1.0%], OR 0.51, 95% CI 0.28-0.93) patients were less likely than White patients (n = 10,440 [1.9%]) to receive DBS. Females were less likely than males to receive DBS for PD (OR 0.69, p < 0.0001) or ET (OR 0.70, p < 0.0001). The authors describe significant racial and sex-based differences in the utilization of DBS for the treatment of PD and ET. Further research is required to ascertain the causes of these disparities, as well as any differences in access to specialty neurosurgical care and referral for neuromodulation approaches.

Validation of the International Classification of Diseases, Tenth Revision-Clinical Modification Diagnostic Code for Essential Tremor.

The positive predictive value (PPV) of the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) code for "essential and other specified forms of tremor" in identifying essential tremor (ET) cases was found to be less than 50%. The ability of the ICD-10-CM G25.0 code for "essential tremor" to identify ET has not been determined. The study objective was to determine the PPV of the G25.0 code. Patients in a tertiary health system with a primary care encounter associated with ICD-10-CM code G25.0 in 2022 underwent medical record review to determine if the consensus criteria from the International Parkinson and Movement Disorder Society for an ET diagnosis were met. 442 patients were included. The PPV of G25.0 in identifying probable ET cases was 74.7% (95% confidence interval (CI) 70.4-78.5%). Among patients prescribed propranolol, the PPV improved to 87.8% (95% CI 78.0-93.6%). Compared to the ICD-9-CM code 333.1, G25.0 is superior for identifying ET cases. A potential limitation of this study is that the consensus criteria applied relies on nonspecific physical exam findings which may lead to an overestimation of the PPV of G25.0. The ICD-10-CM diagnosis code for essential tremor has not been previously validated. The objective of this study was to determine the PPV of the G25.0 code. The PPV in identifying essential tremor cases was 74.7%. The PPV improved among patients prescribed propranolol.

Reduced Bergmann glial process terminations and lateral appendages in essential tremor.

Postmortem examination of the essential tremor cerebellum has revealed a variety of pathological changes centered in and around Purkinje cells. Studies have predominantly focused on cerebellar neuronal connections. Bergmann glial morphology has not yet been studied in essential tremor. Among their many roles, Bergmann glia in the cerebellar cortex ensheath Purkinje cell synapses and provide neuroprotection. Specifically, the complex radial processes and lateral appendages of Bergmann glia are structural domains that modulate Purkinje cell synaptic transmission. In this study, we investigate whether Bergmann glia morphology is altered in the essential tremor cerebellum. We applied the Golgi-Kopsch method and used computerized three-dimensional cell reconstruction to visualize Bergmann glia in the postmortem cerebellum of 34 cases and 17 controls. We quantified morphology of terminal structures (number of terminations and lateral appendage density) and morphology of radial processes (total process length, branch length, branch order, and branch volume) in each glial cell. We quantified number of branches and volume as well. Essential tremor cases had a 31.9% decrease in process terminations and a 35.7% decrease in lateral appendage density in Bergmann glia. Total process length and branch length did not differ between essential tremor cases and controls. We found also a reduction in number of secondary and tertiary branches and tertiary branches volume. These findings suggest that Bergmann glia in essential tremor cases have more alterations in their terminal structures, with a relative preservation of radial processes, and highlight a potential role for these astrocytes in the disease pathophysiology.

Mapping cognitive trajectories in older adults with essential tremor

AbstractBackgroundOlder adults with essential tremor (ET) are at increased risk for Alzheimer’s disease (AD) and related disorders. Examining cognitive trajectories within this population will enable better identification of individuals who evidence accelerated rates of change. Here we examine how variability in baseline cognitive performance affects trajectories of cognitive change within three subgroups of cognitively normal older adults: 1) those whose baseline neuropsychological scores were entirely within normal limits (WNL); 2) those with at least one low score considered to have unlikely clinical significance (UCS); and 3) those with at least one low score considered to have possible clinical significance (PCS).MethodOlder adults with ET completed comprehensive neuropsychological testing and clinical interviews, and 159 received a consensus diagnosis of cognitively normal. Participants were then subdivided into one of three categories defined above: WNL (N = 66, 75.38 ± 8.96 years of age), UCS (N = 54, 76.35 ± 10.25 years), and PCS (N = 37, 80.22 ± 9.00 years). Generalized estimating equations (GEE) were used to compare rates of change in global cognition, memory, executive function, attention, visuospatial, and language z‐scores over time across these groups. Participants were seen for two to four visits (24.98 ± 20.29 months). Models were adjusted for age, gender, and years of education.ResultAll three groups, WNL (β = ‐.005, p = .028), UCS (β = ‐.006, p = .011), and PCS (β = ‐.012, p = .002), evidenced decline in their memory performance over time, with the latter groups declining faster than the WNL group. Relative to the WNL and UCS groups, the PCS group also declined faster over time in overall cognition (β = ‐.010, p = .029) and in language (β = ‐.024, p = .035).ConclusionHeterogeneity in cognitive performance among cognitively normal older adults with ET predicts trajectories of cognitive decline longitudinally. Specifically, rates of decline were slowest in those with entirely normal test scores, and greatest in those whose scores were considered to have possible clinical significance. These preliminary results provide a starting point for further inquiry into the role of nuanced cognitive profiles in predicting rates of decline, impairment, and dementia in ET cases who may initially be labeled as “cognitively normal.”

A prospective cohort study of familial versus sporadic essential tremor cases: Do clinical features evolve differently across time?

BackgroundAlthough essential tremor (ET) is often divided into familial and sporadic cases, few data compare the evolution of clinical features in these groups over time. Leveraging data from a prospective, longitudinal study, we present analyses of the evolution of a broad range of cognitive, motor (i.e., tremor, tandem gait) and other features (e.g., disability) of ET. MethodsSixty-six familial and 23 sporadic ET cases completed in-home evaluations at baseline and 18, 36, and 54-month follow-ups. Assessments included detailed neuropsychological testing and videotaped neurological examinations. Analyses compared the longitudinal course of 16 clinical features in familial and sporadic cases. ResultsBaseline mean age was 75.2 ± 8.8 years and mean observation period was 4.7 ± 0.3 years. Tremor onset age was lower and childhood onset more common in familial than sporadic cases (p's = 0.02). Longitudinal analyses revealed no significant differences between clinical features displayed by familial and sporadic cases, or differences between the patterns of change in clinical features observed in these groups across time. Sporadic cases' daily activity skills declined significantly, whereas familial cases' did not, p's = 0.04 and 0.34, respectively; however, this finding was non-significant when controlling for false discovery rate. Several additional non-significant trends were noted. ConclusionFamilial and sporadic ET cases differed in onset age, and in the prevalence of childhood tremor onset. Although a number of interesting trends were observed, no significant differences in the evolution of clinical features over time in patients with and without a family history of ET were revealed.

Decreased Synaptic Vesicle Glycoprotein 2A Binding in the Human Postmortem Essential Tremor Cerebellum: Evidence of Reduction in Synaptic Density.

Despite being one of the most prevalent neurological diseases, the pathophysiology of essential tremor (ET) is not fully understood. Neuropathological studies have identified numerous degenerative changes in the cerebellum of ET patients, however. These data align with considerable clinical and neurophysiological data linking ET to the cerebellum. While neuroimaging studies have variably shown mild atrophy in the cerebellum, marked atrophy is not a clear feature of the cerebellum in ET and a search for a more suitable neuroimaging signature of neurodegeneration is in order. Postmortem studies in ET have examined different neuropathological alterations in the cerebellum, but as of yet have not focused on measures of generalized synaptic markers. This pilot study focuses on synaptic vesicle glycoprotein 2A (SV2A), a protein expressed in practically all synapses in the brain, as a measure of synaptic density in postmortem ET cases. The current study utilized autoradiography with the SV2A radioligand [18F]SDM-16 to assess synaptic density in the cerebellar cortex and dentate nucleus in three ET cases and three age-matched controls. Using [18F]SDM-16, SV2A was 53% and 46% lower in the cerebellar cortex and dentate nucleus, respectively, in ET cases compared to age-matched controls. In this pilot study, using in vitro SV2A autoradiography, we have observed significantly lower synaptic density in the cerebellar cortex and dentate nucleus of ET cases. Future research could expand on our sample size and focus on in vivo imaging in ET to explore whether SV2A imaging could serve as a much-needed disease biomarker.

Serum Neurofilament Light-Chain Concentrations in Essential Tremor: a Case-Control Study.

Essential tremor (ET) is a common neurological disorder, with clinical and pathophysiological links to the cerebellum. Inquiries into the etiology, pathophysiology, and nosology of ET stand to benefit from the identification of disease biomarkers. Serum neurofilament light chain (NfL) has emerged as a novel signature of conditions in which neuronal injury reflects an outcome of the ongoing disease process. We sought to investigate the concentrations of NfL in ET patients and healthy controls. In this case-control study, our powered study population of 41 ET patients and 40 age-matched healthy controls underwent clinical assessments and measurement of serum NfL concentration using Simoa technology. Serum NfL was elevated in ET patients - mean log-transformed serum NfL concentration = 1.23 ± 0.19 (95% confidence interval [CI] = 1.17-1.29) vs. 1.08 ± 0.15 (95% CI = 1.03-1.13), p = 0.0002. This difference persisted after accounting for age, sex and Montreal Cognitive Assessment score in a multiple linear regression model (p = 0.002) and in an age-matched sample subset of 35 ET cases and 35 controls (p = 0.006). There was no association between tremor severity and serum NfL levels (p = 0.73). In this sample of ET patients and controls, serum NfL concentrations were significantly higher in ET. Studies in additional cohorts of ET cases would be of value in attempting to replicate these results and assessing diagnostic utility.

Cognitive Performance as a Function of MAPT Haplotype: A Prospective Longitudinal Study of an Essential Tremor Cohort.

Cognitive impairment is a feature of essential tremor (ET). There are no studies of the genetic drivers of this association. We examined whether the microtubule-associated protein tau (MAPT) H1 haplotype is associated with cognitive performance in ET. ET cases genotyped for the MAPT H1 and H2 haplotypes completed a battery of neuropsychological tests at baseline and four follow-up evaluations. Chi-square, t-tests, and analyses of covariance examined associations between the presence of the MAPT H1 haplotype, cognitive diagnoses of normal, mild cognitive impairment (MCI), and dementia, and performance in specific cognitive domains. We observed no evidence of cognitive differences as a function of the presence of the MAPT H1 haplotype. Specifically, cases with (n = 57) and without (n = 42) this haplotype did not differ with respect to the prevalence of diagnoses of MCI or dementia, p ≥ 0.87. Moreover, cases with vs without this haplotype did not differ in either the age or point in the disease course at which observed conversions to MCI or dementia occurred, p's ≥ 0.51. Finally, no haplotype-related differences were observed in performance in the cognitive domains of attention, executive function, language, memory, visuospatial or global ability, p's ≥ 0.21, or in changes in performance in these domains across time, p's ≥ 0.08. The study in an ET cohort revealed no influence of MAPT haplotypes on cognitive performance. This study serves as a valuable foundation for future studies to expand our understanding of the genetic drivers of cognitive impairment in ET. This study found no evidence of cognitive differences between individuals with and without the MAPT H1 haplotype. Our work provides a valuable foundation for future work to expand our knowledge of the genetic drivers of cognitive impairment in ET.

Associations between cognitive function and a range of significant life events in an elderly essential tremor cohort study

BackgroundAlthough essential tremor (ET) is associated with cognitive decline, we know little about how specific cognitive changes predict significant events in patients' lives. We examined the relations of attention, executive function, language, memory, and visuospatial performance to the occurrence of near falls, falls, walking aid use, home health aide use, non-independent living and hospitalizations within a prospective, longitudinal study of ET cases. We expected executive function and memory to be most strongly associated with these events. Methods131 ET cases (mean age at baseline = 76.4 ± 9.4 years; 109 normal cognition; 17 mild cognitive impairment, 5 demented) completed questionnaires (clinical history and occurrence of life events) and a battery of neuropsychological tests at baseline and at 18, 36, and 54 months. We assessed associations between cognitive functioning and outcomes via regression equations. ResultsCases with lower baseline levels of executive function reported more near falls, p < 0.006, and were more likely to use a walking aid, p < 0.03, odds ratio (OR) = 2.89 during the follow-up period, than were other cases. Decline in executive function was associated with home health aide use during follow-up, p < 0.04, OR = 3.34. Baseline visuospatial performance also bore a marginally significant association with non-independent living arrangements during follow-up, p < 0.06, OR = 2.13. These effects were independent of age and tremor severity. ConclusionThese data establish the important role that cognitive decline, and executive function specifically, play in the experiences of ET patients. Moreover, these associations are of sufficient magnitude to have significant clinical implications.

Postmortem Cerebellar Volume Is Not Reduced in Essential Tremor: A Comparison with Multiple System Atrophy and Controls.

Essential tremor (ET) is a common movement disorder in which cerebellar microscopic and volume alterations have been repeatedly reported although with disagreement between studies. However, pronounced heterogeneity was found with regard to cerebellar volume alterations. This study aimed to assess postmortem cerebellar volume in subjects with or without ET, as compared with subjects with multiple system atrophy (MSA), a well-established cerebellar neurodegeneration. Cases with ET (n = 29), MSA (n = 7), and non-demented control cases without any movement disorder (n = 22) were selected from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study with annual research-dedicated clinical assessments by neuropsychologists, subspecialist movement disorders, and cognitive/behavioral neurologists, with comprehensive neuropathological examinations after death. Group comparisons were controlled for common age-related neurodegenerative and cerebrovascular pathologies. Cerebellar volumes were calculated using digital images of slices taken at the time of autopsy, immediately after brain removal and before fixation. Cerebellar volume was not reduced in ET subjects compared to controls. The two groups did not differ in terms of incidental cerebrovascular and Alzheimer's disease neuropathology. In contrast, cerebellar volume was significantly reduced in subjects with MSA when compared to ET and control subjects. In a well-characterized cohort, postmortem cerebellar volume measurements suggest that there are no volume alterations in ET when compared to controls, in contrast to significant cerebellar atrophy in subjects with MSA.

Characterizing Lewy Pathology in 231 Essential Tremor Brains from the Essential Tremor Centralized Brain Repository (S51.005)

<h3>Objective:</h3> To address several questions: (1) What proportion of essential tremor (ET) cases exhibit Lewy pathology (LP)? (2) What is the nature (i.e., type, location, severity) of that pathology? (3) How does that pathology relate to various neurodegenerative conditions (e.g., Parkinson’s disease [PD], Alzheimer’s type changes)? (4) What are the clinical correlates of that pathology? <h3>Background:</h3> The aforementioned questions have significant value in terms of furthering our understanding of the biological and mechanistic basis for ET. The Essential Tremor Centralized Brain Repository is the largest repository of prospectively-collected ET brains (n = 231). Hence, we are uniquely poised to address these questions. <h3>Design/Methods:</h3> Each brain had a complete neuropathological assessment, including assessment of LP with alpha-synuclein immunostaining. We created a 10-category classification scheme to fully encapsulate the patterns of LP observed. Four metrics of cerebellar pathology were also quantified. <h3>Results:</h3> Mean age at death = 89.0 ± 6.4 years. Fifty-eight (25.1%) had LP and 46 (19.9%) had early to late stages of pathologic PD. LP was very heterogeneous. Of 58 cases with LP, 14 (24.1%) clinically developed possible PD or PD after a latency of five or more years. There was a similar degree of cerebellar pathology in ET cases both with and without LP. <h3>Conclusions:</h3> One-in-four ET cases had LP, a proportion that in the context of other studies among control populations seems high. LP was heterogeneous, and likely a partial function of observed clinical associations between (1) ET and PD and (2) ET and Alzheimer’s disease, as well as other factors that are unknown. There was evidence of cerebellar degeneration in ET cases both with and without LP, rather than just without. These data have value in terms of furthering our understanding of the biological and mechanistic basis for ET as well as its relatedness to other degenerative diseases. <b>Disclosure:</b> Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health. Dr. Kuo has nothing to disclose. Phyllis Faust has nothing to disclose.

Conversion Rate of Essential Tremor to Essential Tremor-Parkinson’s Disease: Data from a Prospective, Longitudinal Study (S42.010)

<h3>Objective:</h3> We quantified the conversion rate from essential tremor (ET) to ET with Parkinson’s disease (ETPD) in a prospective, longitudinal cohort study of ET cases. We compared the observed rate to that reported in the epidemiological literature. <h3>Background:</h3> There has been a longstanding dialogue as to whether ET increases the risk of developing PD. While there are relevant cross-sectional data, there are almost no longitudinal, prospective data. <h3>Design/Methods:</h3> We enrolled ET cases in a prospective, longitudinal study. A senior movement disorders neurologist evaluated standardized neurological examinations every 18 months. <h3>Results:</h3> 193 ET cases (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 ET cases 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 (males, ≥40 years) and 37.55 (females, ≥40 years). The incidence/100,000 py in males peaked in the 80 – 89 year old age group (258.47) and in females in the 80 – 89 year old age group (103.48 py). The above published values are 3.4 – 23.5 times lower than the value we observed for ET. <h3>Conclusions:</h3> The 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. <b>Disclosure:</b> Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health. Dr. Berry has nothing to disclose. Dr. Ghanem has nothing to disclose. Dr. Cosentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Association for Frontotemporal Dementia. Dr. Cosentino has received personal compensation in the range of $500-$4,999 for serving as a Consultant for SAGE Pharmaceuticals.

Serum Neurofilament Light-chain Concentrations in Essential Tremor: A Case-Control Study (P7-11.003)

<h3>Objective:</h3> We sought to investigate the concentrations of neurofilament light chain (NfL) in essential tremor (ET) patients and healthy controls. <h3>Background:</h3> Inquiries into the etiology, pathophysiology, and nosology of essential tremor (ET) stand to benefit from the identification of disease biomarkers. Serum neurofilament light chain (NfL) has emerged as a novel signature of conditions in which neuronal injury reflects an outcome of the ongoing disease process. <h3>Design/Methods:</h3> In this cross-sectional, case-control, observational study, 41 ET patients and 41 healthy controls underwent clinical assessments and measurement of serum NfL concentration using Simoa technology. <h3>Results:</h3> Serum NfL was elevated in ET patients (median = 16.6 pg/mL) versus controls (median = 11.3pg/mL) (p &lt;0.001). NfL concentrations remained higher in ET patients than controls after stratification by sex (p = 0.006 and 0.02, for female and male participants, respectively). This difference persisted after accounting for age, sex and Montreal Cognitive Assessment score in a multiple linear regression model (p = 0.00947, Benjamini-Hochberg correction). <h3>Conclusions:</h3> In this sample of ET patients and controls, serum NfL concentrations were significantly higher in ET. Studies in additional cohorts of ET cases would be of value in attempting to replicate these results and assessing diagnostic utility. <b>Disclosure:</b> The institution of Dr. Salinas has received research support from North Texas VA Health Care System New Investigator Award. The institution of an immediate family member of Dr. Salinas has received research support from Veterans Health Administration. Nora Hernandez has nothing to disclose. Dr. Louis has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wolters Kluwer - Merritt’s Textbook of Neurology. The institution of Dr. Louis has received research support from National Institutes of Health.

Limb positioning and magnitude of postural tremor ratings: A study of 100 essential tremor cases

BackgroundEssential tremor (ET) is a highly prevalent movement disorder. As the diagnosis is purely clinical, it is important for clinicians to develop a reliable taxonomy of signs and symptoms of ET. Here, we investigate two common clinical maneuvers for determining the presence and severity of postural tremor in ET cases: the evaluation of tremor observed when arms are held in the outstretched and wing posture positions. MethodsTwo movement disorders neurologists assessed tremor severity from videotaped neurological evaluations of 100 ET cases displaying outstretched and wing posture positions. These raters also completed a forced choice measure indicating whether upper limb tremor was more severe in the outstretched position, the wing posture position, or equivalent in the two positions. ResultsOur raters judged tremor observed in the wing posture position to be more severe than tremor observed in the outstretched position (average ratings of 1.17 and 1.03, respectively, p‘s <0.05). This finding replicated across the two independent neurologists’ ratings of tremor severity. Analyses of the forced choice measure revealed parallel results, with tremor observed in the wing posture position more often identified as more severe than tremor observed in the outstretched position (37.5% versus 14.5%, respectively, p < 0.05). ConclusionOur data reveal that ET cases generally display more severe upper limb tremor in the wing posture position than in the outstretched position. These findings having potential clinical and research implications, suggesting that postural tremor in ET may be more easily identified from observations of the wing posture than the outstretched position.

Reliability of Self-Report Data on Age of Onset in Essential Tremor: Data from a Prospective, Longitudinal Cohort

Background: Essential tremor (ET) is a highly prevalent neurological disease. Age of onset can occur anytime between childhood and advanced age. Tremor generally starts insidiously. Age of onset is a particularly important data item in clinical and epidemiological research. In general, these data are self-reported by ET cases. A fundamental question is whether ET cases reliably report their age of onset. Methods: In this prospective, epidemiological study of 125 ET cases, self-reported age of onset data were collected at regular 18 months intervals over four time points. Results: The correlation between self-reported age of onset was high – intra-class correlation coefficient = 0.972 (95% confidence interval = 0.962–0.980, p < 0.001). However, agreement was not perfect. Approximately 20–25% of participant’s reports at different time intervals differed by as much as 10 years, and approximately 10% of participant’s reports differed by as much as 20 years. Conclusions: There was a robust correlation between self-reports of age of onset. Yet in a not-insignificant number of cases, there were considerable differences, some of which were substantial. These findings have broad implications for development of diagnostic algorithms, data stratification schemes, and analyses that assess correlations between biomarker data and clinical features (e.g., disease duration).