Essential Tremor Symptoms Research Articles

REM sleep behavior disorder and Prodromal Parkinson’s Disease in patients with Essential Tremor

Several studies suggested the presence of non-motor symptoms in Essential Tremor (ET), including REM sleep behavioral disorder (RBD). RBD is an essential criterion for Prodromal Parkinson's Disease (PPD), suggesting a link between ET and PD. Our objective was to assess the prevalence and features of ET patients with RBD and PDD.RBD was diagnosed by questionnaire screening, followed by polysomnography. PPD risk factors and prodromic markers were assessed with a structured protocol. Patients were characterized regarding tremor features. ET patients with RBD (ET-RBD) and PPD (ET-PPD) were compared to patients without RBD (ET-nonRBD) and without PPD (ET-nonPPD), respectively. ET-RBD patients were also compared with a group of isolated RBD (iRBD) regarding PPD features.We assessed a total of 64 ET patients. Five (8.3 %) and 4 (6.3 %) had criteria for RBD and PPD, respectively. ET-RBD patients did not differ from ET-nonRBD except for a higher prevalence of PPD. There were no significant differences between ET-RBD and iRBD (n = 12) groups. ET-PPD had a higher prevalence of positive DaT-Scans and RBD compared to ET-nonPPD. Three ET-RBD patients had PPD and 3 ET-PPD had RBD.Both RBD and PPD are more frequent in ET patients than in general aged population but not related with specific tremor features. ET-RBD patients did not differ significantly from iRBD patients, a group prone to develop PD. These data suggest a link between ET and PD and are in accordance with studies showing an increase incidence of lewy-body pathology and PD in ET populations.

Intelligent devices for assessing essential tremor: a comprehensive review.

Essential tremor (ET) stands as the most prevalent movement disorder, characterized by rhythmic and involuntary shaking of body parts. Achieving an accurate and comprehensive assessment of tremor severity is crucial for effectively diagnosing and managing ET. Traditional methods rely on clinical observation and rating scales, which may introduce subjective biases and hinder continuous evaluation of disease progression. Recent research has explored new approaches to quantifying ET. A promising method involves the use of intelligent devices to facilitate objective and quantitative measurements. These devices include inertial measurement units, electromyography, video equipment, and electronic handwriting boards, and more. Their deployment enables real-time monitoring of human activity data, featuring portability and efficiency. This capability allows for more extensive research in this field and supports the shift from in-lab/clinic to in-home monitoring of ET symptoms. Therefore, this review provides an in-depth analysis of the application, current development, potential characteristics, and roles of intelligent devices in assessing ET.

Insight into the Relationship Between Motor and Cognitive Symptoms in Essential Tremor

Essential tremor (ET) is a heterogeneous disorder characterized by bilateral upper limbs action tremor and, possibly, neurological signs of uncertain significance, including voluntary movement abnormalities and cognitive disturbances, i.e., the so-called ‘soft’ signs configuring the ET-plus definition. While motor and cognitive disturbances often coexist in ET, their interrelationship remains largely unexplored. Here we aim to further investigate the relationship between motor symptoms, objectively assessed through kinematic analysis, and cognitive dysfunctions in ET. Seventy ET patients underwent clinical examination, as well as kinematic recordings of tremor and finger tapping and a thorough cognitive assessment. We then tested clinic-demographic and kinematic differences between patients with and without cognitive abnormalities, i.e., with mild cognitive impairment (MCI). Correlation analysis served to explore potential associations between kinematic and cognitive data. Forty-three ET patients (61.42%) had MCI. ET-MCI patients exhibited reduced movement velocity during finger tapping compared to those with normal cognition (p < 0.001). Lower movement velocity during finger tapping was associated with poorer cognitive performance. Namely, we observed a correlation between movement velocity and performance on the Babcock Story Immediate and Delayed Recall Test (r = 0.52 and r = 0.45, both p < 0.001), as well as the interference memory task at 10 and 30 s (r = 0.3, p = 0.008 and r = 0.2, p = 0.03). In this study, we have provided data for a better pathophysiological interpretation of motor and cognitive signs in ET, including the role played by the cerebellum or extra-cerebellar areas, which possibly underpin both signs.

Resveratrol and 1,25-dihydroxyvitamin D decrease Lingo-1 levels, and improve behavior in harmaline-induced Essential tremor, suggesting potential therapeutic benefits

Essential tremor (ET) is a neurological disease that impairs motor and cognitive functioning. A variant of the Lingo-1 genetic locus is associated with a heightened ET risk, and increased expression of cerebellar Lingo-1. Lingo-1 has been associated with neurodegenerative processes; however, neuroprotection from ET-associated degeneration can be conferred by the protein Sirt1. Sirt1 activity can be promoted by Resveratrol (Res) and 1,25-dihydroxyvitamin D3 (VitD3), and thus these factors may exert neuroprotective properties through a Sirt1 mechanism. As Res and VitD3 are linked to Sirt1, enhancing Sirt1 could counteract the negative effects of increased Lingo-1. Therefore, we hypothesized that a combination of Res-VitD3 in a harmaline injection model of ET would modulate Sirt1 and Lingo-1 levels. As expected, harmaline exposure (10 mg/kg/every other day; i.p.) impaired motor coordination, enhanced tremors, rearing, and cognitive dysfunction. When Res (5 mg/kg/day; i.p.) and VitD3 (0.1 mg/kg/day; i.p.) were given to adult rats (n = 8 per group) an hour before harmaline, tremor severity, rearing, and memory impairment were reduced. Individual treatment with Res and VitD3 decreased Lingo-1 gene expression levels in qPCR assays. Co-treatment with Res and VitD3 increased and decreased Sirt1 and Lingo-1 gene expression levels, respectively, and in some cases, beneficial effects on behavior were noted, which were not seen when Res or VitD3 were individually applied. Taken together, our study found that Res and VitD3 improved locomotor and cognitive deficits, modulated Sirt1 and Lingo-1. Therefore, we would recommend co-treatment of VitD3 and Res to leverage complementary effects for the management of ET symptoms.

Voice Analysis in Patients with Essential Tremor

The objective of this study was to reveal the phonetic characteristics of patients with or without voice tremor in patients with essential tremor (ET), determine whether these phonetic features are ET specific, and test the influence of ET on vocal tremor. The study included a total of 30 patients with ET and 29 healthy volunteers. The severity of ET was evaluated using the Washington Heights Inwood Genetic Study of Essential Tremor (WHIGET) tremor rating scale. Patients with major tremor complaints for at least 3years, WHIGET scoring scores below 15, and patients newly diagnosed in our clinic and for whom drug therapy has not yet been started were selected. A total of 59 participants (n=34 with ET and n=25 as control) were included in the study. The ages of the participants ranged from 20 to 82years, with a mean age of 54.50±15.04years. The gender distribution was 57.6% male and 42.4% female, and there was no statistically significant difference between the two groups in terms of age and gender. The study found that individuals with ET had significantly higher jitter, shimmer, S/Z, Pataka, frequency tremor intensity index, amplitude tremor intensity index, and frequency tremor power index values than the control group. However, there was no statistically significant difference between the two groups in terms of MPT, frequency tremor cyclicality, amplitude tremor cyclicality, frequency tremor frequency, and amplitude tremor frequency values. Our study shows that, even in the absence of essential voice tremor, there is an effect of ET on voice quality. These findings contribute to the understanding of the nonmotor symptoms of ET and may aid in the diagnosis and management of this condition. Further research is needed to explore the potential use of acoustic analysis parameters in the diagnosis and monitoring of ET.

Tremor Reduction using DBS: Outcomes of a Real-world, Prospective, Multicenter Essential Tremor Registry (P7-11.004)

<h3>Objective:</h3> To evaluate outcomes of directional DBS systems with Multiple Independent Current Control (MICC) technology when implanted in patients with Essential Tremor (ET) as standard of care. <h3>Background:</h3> ET is one of the most common neurological diseases affecting about 0.9% of the world population. Medical treatment is focused on management of motor symptoms, and therapeutic options include pharmacotherapy, ventral intermediate nucleus (Vim) thalamotomy, and/or thalamic Deep Brain Stimulation (DBS). Currently, Vim DBS is recommended as a therapeutic option for appropriate subjects with ET (Wharen 2017, Zesiewicz 2005). <h3>Design/Methods:</h3> In this prospective, on-label, multi-center, international DBS registry, enrolled patients are implanted with a directional MICC-based DBS system (Vercise, Boston Scientific). Patients are followed up to 3-years where overall improvement in quality of life and ET symptoms are evaluated. Adverse events are also being collected. <h3>Results:</h3> To date, 30-patients have been implanted (age = 64.8 ± 15.1 years [Mean (SD)], 53.1% male) with a mean disease duration of 19.3-years. A 17.3-point change in QUEST Summary Index was noted at 12-months representing a clinically significant difference (&gt;4.47-point change) (Pinter 2019). In addition, a mean 9-hours of tremor reduction in a typical day was noted (14.7-hours at Baseline versus 6.5-hours at 12-months). Moreover, based on the severity scale of FTMTRS, when comparing disability at 12-months (vs Baseline), no patient reported experiencing marked disability (vs. 9.4% at Baseline), 16.7% reported moderate disability (vs. 81.3% at Baseline) and 83.3% reported mild disability (vs 9.4% at Baseline). <h3>Conclusions:</h3> Preliminary results from this ongoing registry show clinically important outcomes in quality of life, as well as motor function, thereby reflecting improvement in overall disability among patients (i.e., a disability profile moving from moderate/severe to more mild/moderate disability). This registry represents the first comprehensive, large-scale collection of real-world outcomes with MICC-based DBS systems for ET. <b>Disclosure:</b> Dr. Deuschl has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Boston Scientific Cavion Functional Neuromodulation. The institution of Dr. Deuschl has received research support from Medtronic. Dr. Deuschl has received publishing royalties from a publication relating to health care. Dr. Loret has nothing to disclose. The institution of Norbert Kovacs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. The institution of Norbert Kovacs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbott. The institution of Norbert Kovacs has received personal compensation in the range of $500-$4,999 for serving as a Consultant for boston Scientific. Norbert Kovacs has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Norbert Kovacs has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Hungarian Scientific Parkinson’s Disease Society. The institution of Norbert Kovacs has received research support from Abbott. The institution of Norbert Kovacs has received research support from Hungarian National Research Board. Dr. Clement has nothing to disclose. P.R. Schuurman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Boston Scientific. P.R. Schuurman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medtronic.

510 Prospective, Multicenter, International Outcomes Study of Deep Brain Stimulation for Essential Tremor

INTRODUCTION: Essential Tremor (ET) treatment is focused on medical management of motor symptoms and includes pharmacotherapy and ventral intermediate nucleus (VIM) thalamotomy, which is being largely replaced by thalamic Deep Brain Stimulation (DBS) as the surgical treatment of choice. DBS of the VIM thalamus is recommended as a therapeutic option for appropriate subjects with ET (Elble RJ., et al. Expert Rev Neurother. 2018). METHODS: This is a prospective, on-label, multi-center, international DBS outcomes study conducted at up to 50 implanting centers. All participants are implanted with a multiple-source, constant-current directional DBS system (Vercise, Boston Scientific). Subjects are followed for up to 3-years post implantation where their overall improvement in quality of life and ET symptoms are evaluated. Clinical endpoints evaluated at baseline and follow-up timepoints include: The Essential Tremor Rating Assessment Scale (TETRAS), Quality of Life in Essential Tremor Questionnaire (QUEST), Fahn-Tolosa-Marin Rating Scale (TRS), and Global Impression of Change. Adverse events also collected. RESULTS: To date, 18-implanted subjects with a mean disease duration of 15.1 ± 14.6-years and a baseline QUEST Summary Index score of 35.0 ± 12.4. At 6-months post-DBS, a clinically significant improvement in quality of life (∆ = 19.5-point change in QUEST SI score) was reported. In addition, a mean 9-hours of tremor reduction was noted (14-hours at Baseline, 6.9-hours at 6-months) in a typical day at 6-months. All subjects (100%) reported mild disability, and no subject reported moderate or marked disability (89% at baseline) as reported by TRS at 6 months. CONCLUSIONS: This work represents the first comprehensive, large scale collection of real-world outcomes and evaluation of safety and effectiveness of a multiple-source, constant-current DBS system capable of providing directionality for use in treatment of Essential Tremor.

Depression Scores following Ventral Intermediate Nucleus Deep Brain Stimulation for Essential Tremor: A Meta-Analysis

Background: Essential tremor (ET) patients present with both motor and non-motor symptoms including depression. Although deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) is used to treat motor symptoms of ET, there is no consensus as to how VIM DBS influences non-motor symptoms, specifically depression. Objective: The objective of this study was to conduct a meta-analysis of available studies investigating change in pre- to postoperative depression scores as measured by Beck Depression Inventory (BDI) in ET patients receiving VIM DBS. Methods: Inclusion criteria were randomized control trials or observational studies of patients undergoing unilateral/bilateral VIM DBS. Non-ET patients, case reports, patients <18 years old, only non-VIM electrode placement, non-English articles, and abstracts were excluded. The primary outcome was change in BDI score from the preoperative time point to the last available follow-up. Pooled estimates of overall effect for BDI standardized mean difference were calculated using random effects models with the inverse variance method. Results: Seven studies divided into eight cohorts for a total of 281 ET patients met inclusion criteria. Pooled preoperative BDI score was 12.44 (95% CI [6.63–18.25]). A statistically significant decrease in depression scores was observed postoperatively (SMD = −0.29, 95% CI [−0.46 to −0.13], p = 0.0006). Pooled postoperative BDI score was 9.18 (95% CI [4.98–13.38]). A supplementary analysis which included an additional study with an estimated standard deviation at last follow-up was conducted. There was also a statistically significant decrease in depression postoperatively (9 cohorts, n = 352, SMD = −0.31, 95% CI [−0.46 to −0.16], p < 0.0001). Conclusions: Both quantitative and qualitative analyses of the existing literature suggest that VIM DBS improves depression postoperatively among ET patients. These results may guide surgical risk-benefit analysis and counseling for ET patients undergoing VIM DBS.

Why is Essential Tremor so Difficult to Treat? A Literature Review

Essential tremor (ET) is the most common movement disorder and affects tens of millions of individuals worldwide. It is characterized by isolated upper-limb tremors for at least three years without other neurological signs or tremors in other locations. Despite ET being a widespread movement disorder, its etiology and pathophysiology are poorly understood. This lack of understanding poses significant challenges towards the development of treatments and cures. There is no cure for ET, and current treatments for ET are limited and are often insufficient. ET symptoms can differ greatly between patients, and phenotyping is the only method for diagnosis. ET often overlaps with other disorders including dystonia and Parkinson’s disease, which further complicates diagnosis and treatment. Current treatments begin with pharmacotherapy, and progress to surgical options in drug-resistant patients. There is ongoing research into non-invasive electrical stimulation treatments that may prove to be safe and effective; however, further research is needed. The aim of this review is to assess the literature and summarize why ET is so difficult to treat. We evaluate the efficacy of current treatments, and the potential of future treatments. We summarize four reasons why ET remains so difficult to treat: 1) the unknown etiology and pathophysiology, 2) the lack of a suitable animal model, 3) difficulties with diagnosis, and 4) absence of personalized treatments. Despite the current challenges, ET remains an active area of research and novel experimental treatments may produce safe and effective non-invasive therapeutic options for ET.

Differential contributions of depression, apathy, and anxiety to neuropsychological performance in Parkinson’s disease versus essential tremor

ABSTRACT Introduction Mood symptoms are common features of Parkinson’s disease (PD) and essential tremor (ET) and have been linked to worse cognition. The goals of the present study were to compare the severity of anxiety, apathy, and depressive symptoms in PD, ET, and healthy controls (HC) and to examine differential relationships between mood and cognition. Method Older adults with idiopathic PD (N = 448), ET (N = 128), or HC (N = 136) completed a multi-domain neuropsychological assessment consisting of memory, executive function, and attention/working memory domains. Participants also completed self-reported mood measures. Between-group differences in mood and cognition were assessed, and hierarchical regression models were conducted to examine relationships between mood and cognition in each group. Results Relative to the HC group, the PD and ET groups reported more mood symptoms and scored lower across all cognitive measures. There were no differences between the two movement disorder groups. Mood variables explained 3.9–13.7% of the total variance in cognitive domains, varying by disease group. For PD, apathy was the only unique predictor of executive function (β = −.114, p = .05), and trait anxiety was the only unique predictor of attention/working memory (β = −.188, p < .05). For ET, there were no unique predictors, though the overall models significantly predicted performance in the executive function and attention/working memory domains. Conclusions In a large cohort of ET and PD, we observed that the two groups had similar self-reported mood symptoms. Mood symptoms were differentially associated with cognition in PD versus ET. In PD, increased apathy was associated with worse executive function and higher trait anxiety predicted worse attention/working memory. For ET, there were no unique predictors, though the overall mood symptom severity was related to cognition. Our study highlights the importance of considering the relationship between mood and neuropsychological performance in individuals with movement disorders.

Rationale and Evidence for Peripheral Nerve Stimulation for Treating Essential Tremor.

Background:There is growing recognition of peripheral stimulation techniques for controlling arm symptoms in essential tremor (ET). Recently, the FDA gave clearance to the Cala system, a device worn around the wrist to treat arm tremors. The Cala system stimulates the sensory afferents of the peripheral nerves with high-frequency pulses. These pulses are delivered to the median and radial nerves alternately at the tremor frequency of the individual patient.Methods:The PubMed database was searched using the terms (“Essential Tremor”[Mesh] OR “essential tremor” [Title/] OR “tremor” [Title/]) AND (“peripheral arm stimulation” [Title/] OR “Cala device” [Title/] OR “sensory afferent stimulation” [Title/] OR “afferent stimulation” [Title/] OR “arm stimulation” [Title/] OR “peripheral nerve stimulation” [Title/]).Results:The search yielded 54 articles. Many studies discussed the rationale and various strategies for peripheral modulation of tremor. While the Cala system was found to be safe and well-tolerated in ET, data on efficacy revealed mixed findings. In a large randomized, blinded trial (n = 77), the primary outcome evaluated with spiral drawing task did not improve but the secondary outcomes reflected by the arm tremor severity and the activities of the daily living score revealed 20–25% improvements. A subsequent trial (n = 323) found that the in-home use of the Cala device led to improvements of similar magnitude lasting for at least three months but the clinical assessments were open-labeled.Discussion:Peripheral stimulation techniques are promising therapeutic modalities for treating ET symptoms. Stimulation of sensory afferent nerve fibers at the wrist can potentially modulate the peripheral and central components of the tremor network. Although the Cala system is user-friendly, safe, and well-tolerated, the current clinical evidence on the efficacy is inconsistent and insufficient. Thus, more data is warranted for implementing peripheral nerve stimulation as a standard of care for ET.HighlightsThe current review discusses the rationale, background, and potential mechanisms for using peripheral arm stimulation devices for treating ET. The Cala system is a wrist-worn peripheral nerve stimulation device that received FDA clearance to treat arm tremors. The current review evaluates the evidence for the safety and efficacy of using the Cala system and similar devices in clinical practice.

Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor

ObjectivesTo determine change in restless legs syndrome (RLS) symptoms in essential tremor (ET) patients undergoing bilateral thalamic ventral intermedius (VIM) deep brain stimulation (DBS) surgery. Materials and MethodsWe retrospectively reviewed our database of ET patients with RLS who had undergone VIM DBS for tremor from 2012 to 2020. We reviewed the patients with available International Restless Leg Syndrome Study Group RLS scale scores before and after DBS. Percentage of responders, defined as proportion of patients experiencing three or more point improvement of RLS scores post-DBS, was calculated. We performed two-tailed t-test of pre-DBS and post-DBS RLS scores. ResultsWe identified 13 patients with ET and RLS who had undergone bilateral VIM DBS, of whom nine (69%) were responders post-DBS. Five of 13 patients (38%) had complete resolution of RLS post-DBS. For all patients, mean pre-DBS RLS score was 15.8 ± 7.9 which improved by 46% post-DBS to a mean of 8.5 ± 8.8 (p = 0.007). Four patients rated their RLS scale one night with the stimulator OFF and another night with the stimulator ON. The mean RLS score with stimulator ON was 15.5 ± 7.6 which improved by 53% to a mean of 6.25 ± 7.8 (p = 0.008), with two having complete resolution of RLS with stimulator ON. Of the nine responders, six preferred to keep their stimulator ON at night due to relief of RLS and better subjective quality of sleep. ConclusionsWe report for the first time improvement of RLS in patients with ET after bilateral thalamic DBS. Although many ET patients with nonrechargeable DBS systems switch off their stimulator at night to conserve battery life, those with RLS may potentially benefit from keeping their stimulator ON at night to relieve their RLS.

Longitudinal Progression of Essential Tremor: Do Tremor Severity Scores Increase at a Uniform Rate?

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.

Combined Intrinsic Local Functional Connectivity With Multivariate Pattern Analysis to Identify Depressed Essential Tremor.

BackgroundAlthough depression is one of the most common neuropsychiatric symptoms in essential tremor (ET), the diagnosis biomarker and intrinsic brain activity remain unclear. We aimed to combine multivariate pattern analysis (MVPA) with local brain functional connectivity to identify depressed ET.MethodsBased on individual voxel-level local brain functional connectivity (regional homogeneity, ReHo) mapping from 41 depressed ET, 43 non-depressed ET, and 45 healthy controls (HCs), the binary support vector machine (BSVM) and multiclass Gaussian Process Classification (MGPC) algorithms were used to identify depressed ET patients from non-depressed ET and HCs, the accuracy and permutations test were used to assess the classification performance.ResultsThe MGPC algorithm was able to classify the three groups (depressed ET, non-depressed ET, and HCs) with a total accuracy of 84.5%. The BSVM algorithm achieved a better classification performance with total accuracy of 90.7, 88.64, and 90.48% for depressed ET vs. HCs, non-depressed ET vs. HCs, and depressed ET vs. non-depressed ET, and the sensitivity for them at 80.49, 76.64, and 80.49%, respectively. The significant discriminative features of depressed ET vs. HCs were primarily located in the cerebellar-motor-prefrontal gyrus-anterior cingulate cortex pathway, and for depressed ET vs. non-depressed ET located in the cerebellar-prefrontal gyrus-anterior cingulate cortex circuits. The partial correlation showed that the ReHo values in the bilateral middle prefrontal gyrus (positive) and the bilateral cerebellum XI (negative) were significantly correlated with clinical depression severity.ConclusionOur findings suggested that combined individual ReHo maps with MVPA not only could be used to identify depressed ET but also help to reveal the intrinsic brain activity changes and further act as the potential diagnosis biomarker in depressed ET patients.

Epidemiology of pediatric essential tremor in the United States: a systematic literature review from 2010 to 2020

Background:Essential tremor (ET) is one of the most common movement disorders worldwide, yet the size of the pediatric ET population is not well understood. The objective of this review was to identify, evaluate, and synthesize evidence describing the epidemiology of pediatric ET in the United States published between 2010 and 2020.Methods:The authors searched MEDLINE, Embase, and the Cochrane Database of Systematic Reviews using terms related to ET, epidemiology, and pediatric patients. Eligibility criteria included observational studies that reported primary data on pediatric prevalence or incidence of ET or age of onset/diagnosis of ET. A total of 562 unique articles were identified for screening.Results:The review did not identify any studies that reported information on pediatric prevalence or incidence of ET, or age of ET diagnosis among nonpediatric patients. A total of 10 samples were identified, all of which described age of ET onset that ranged from 27.0 years to 56.7 years among 9 adult populations (weighted mean of 41.6 years) and 9.7 years in a single pediatric sample. One adult sample reported that 13% of all ET cases reported onset by age 14, and 21.8% of all ET cases reported onset by age 18.Discussion:There is a notable lack of recent data describing the incidence and prevalence of pediatric ET in the United States. Many children who present with symptoms of ET may not be diagnosed until later in life, and an increased awareness of pediatric ET could allow for early identification and monitoring of these patients.

P 23 The overlap of lesions placed by MRIgFUS with the cerebellothalamic tract does not adequately explain symptom control in ET

Background: The thalamic ventral intermediate (Vim) nucleus is part of a network that appears to be disrupted in essential tremor (ET) and is the most relevant target of functional neurosurgery to alleviate ET symptoms. As the most important afferent of the VIM, the cerebellothalamic tract (CTT) transmits information from cerebellar nuclei. Disruption of this tract - in the past via subthalatomies and in the present via deep brain stimulation is considered the best option of tremor treatment, partly because of the high anatomical density of CTT fibers before entering the VIM, and partly because of the greater distance to sensory thalamic nuclei. Recently, initial pilot studies have also documented transcranial MRI-guided high-intensity focused ultrasound (MRIgFUS) as an effective treatment modality. Unilateral MRIgFUS lesioning was highly efficacious in reducing contralateral hand tremor in ET with mild and transient adverse effects. However, targeting of MRIgFUS has so far been based on MRI imaging without dedicated evidence of the underlying connectome. Here, we test a method for quantitative analysis of the involved fiber tracts and test whether the measured clinical effect correlates with overlap of the set lesion with individual fiber tracts, such as CTT. Materials and Methods: We revisited pre- and post-procedural MRIs of 6 ET patients (Øage 70,7 (± 8,5) years , Ø Tremor rating (TR) (pre): 43,8 (± 9,8)) who underwent unilateral ablation of the CTT by MRIgFUS. The images, obtained 48 hours (48H) and 3-6 months (3M+) after the procedure, were used to create 3D-models of the lesions which were localized within MNI-space with the pre-procedural MRI and atlas registration using Suretune®. The models were subsequently used to calculate interferences with fiber tracts. A linear model was employed to assess the correlation between the quantitative interference and improvement of the clinical score at two timepoints after the procedure (48H, n=6: TR: 16,7 (±5,5) ; 3M+, n= 5: TR: 19,2 (±7,2)). Results: The lesions volume differed between the 48H (Ø 281.78mm3(±77.77), n=6) and 3M+(Ø 53.82mm3(±22), n=5) conditions (p<0.01). After 48H primarily the CTT (Ø72,4 % (±34)) but also the M1 (Ø36,05 % (±43)) interfered, while after 3M+ the overlap reduced tremendously for the CTT (Ø1% (±1,6), p=0.017) and slightly for the M1(Ø26,7% (±28,4), p=0.67). Preliminary results could not show a correlation between the observed clinical improvement with the interference of the lesions with a specific tract. Discussion: Interestingly, there is no clear correlation between clinical outcome and the overlap between the lesion placed by MRIgFUS and the fibers of the CTT. This might indicate that the observed clinical effect would have to be explained only partially by the targeted CTT but also by other fiber tracts. The data set was too small for a meaningful multivariate regression analysis, but pooling data sets from different centers may mean a solution to this problem in the future.

Does essential tremor increase risk of cognitive impairment and dementia? Yes.

Essential Tremor (ET), by definition, is a disorder of movement. Yet over the years, epidemiologic, clinical, pathologic, and neuroimaging studies have converged to reveal a cognitive side of ET. The cognitive symptoms in ET are heterogeneous and are likely to reflect heterogeneous underlying mechanisms. In this chapter, we review and synthesize a diverse set of studies from both population-based settings to cohorts with more detailed investigations into cognition to consider the various mechanisms by which cognitive symptoms may emerge in a subset of individuals with ET. As part of our analysis, we consider questions surrounding ET diagnosis and the possibility of comorbid disease as potential factors that, upon closer examination, appear to strengthen the argument in favor of ET as a risk factor for dementia. Importantly, we also consider the clinical relevance of cognitive impairment in ET. While ET is not universally characterized by significant cognitive deficits, the data from epidemiological, cognitive, neuroimaging, and postmortem neuropathologic studies converge to reveal an increased risk for cognitive impairment and dementia among individuals with ET. We conclude by offering directions for future research, and a neurocognitive framework with which to consider existing findings and to use in the design of novel studies dedicated to clarifying the basis, nature, and course of cognitive impairments in ET.

Identifying Depressed Essential Tremor Using Resting-State Voxel-Wise Global Brain Connectivity: A Multivariate Pattern Analysis.

Background and Objective: Although depression is one of the most common non-motor symptoms in essential tremor (ET), its pathogenesis and diagnosis biomarker are still unknown. Recently, machine learning multivariate pattern analysis (MVPA) combined with connectivity mapping of resting-state fMRI has provided a promising way to identify patients with depressed ET at the individual level and help to reveal the brain network pathogenesis of depression in patients with ET.Methods: Based on global brain connectivity (GBC) mapping from 41 depressed ET, 49 non-depressed ET, 45 primary depression, and 43 healthy controls (HCs), multiclass Gaussian process classification (GPC) and binary support vector machine (SVM) algorithms were used to identify patients with depressed ET from non-depressed ET, primary depression, and HCs, and the accuracy and permutation tests were used to assess the classification performance.Results: While the total accuracy (40.45%) of four-class GPC was poor, the four-class GPC could discriminate depressed ET from non-depressed ET, primary depression, and HCs with a sensitivity of 70.73% (P < 0.001). At the same time, the sensitivity of using binary SVM to discriminate depressed ET from non-depressed ET, primary depression, and HCs was 73.17, 80.49, and 75.61%, respectively (P < 0.001). The significant discriminative features were mainly located in cerebellar-motor-prefrontal cortex circuits (P < 0.001), and a further correlation analysis showed that the GBC values of significant discriminative features in the right middle prefrontal gyrus, bilateral cerebellum VI, and Crus 1 were correlated with clinical depression severity in patients with depressed ET.Conclusion: Our findings demonstrated that GBC mapping combined with machine learning MVPA could be used to identify patients with depressed ET, and the GBC changes in cerebellar-prefrontal cortex circuits not only posed as the significant discriminative features but also helped to understand the network pathogenesis underlying depression in patients with ET.

Follow-up evaluation of motor and non-motor symptoms in essential tremor

Essential Tremor (ET) is a common and heterogeneous movement disorder characterized by action tremor of upper limbs and other body parts, as well as non-motor symptoms (e.g., cognitive and psychiatric abnormalities). However, only few studies have attempted to estimate symptoms progression in ET.

Эссенциальный тремор - не просто тремор (обзор литературы)

Essential tremor is one of the most common movement disorders. The nature of this disease is not fully understood. It was believed that this pathology manifests itself only by tremor, and symptoms such as depression, anxiety and apathy in patients with essential tremor can only be regarded as a reaction to the presence of tremor. Cognitive impairment is a concomitant pathology that can occur in the elderly, which accounts for a more frequent onset of the disease. But is it really so Purpose of the study. To study the literature data to identify the presence in patients with essential tremor of such signs that can be attributed to the group of "non-motor" symptoms. Material and methods. In order to study the literature data, a search was carried out in the Web of Science, PubMed databases. During the search, all articles published since 2000 were examined and the following terms were used in combination with "essential tremor": "non-motor symptoms", "anxiety", "depression", "apathy", "cognitive impairment", "sleep disorders", "hearing impairment", "hyposmia". The main search terms were studies based on the study of patients with essential tremor: meta-analyzes, original studies, retrospective and cohort studies. Results and discussion. It can be unambiguously argued that symptoms such as anxiety, depression, apathy and cognitive, hearing and smell dysfunctions are characterised to the patients with essential tremor. The first three manifestations were attributed to the response to the presence of tremor. And cognitive functions, hearing and smell dysfunctions was considered a concomitant pathology, which occurs quite often in old age, which accounts for a more frequent onset of the disease. But in reality, everything is not so simple. The literature data, which began to appear over the past 20 years, make it clear that the previously mentioned clinical manifestations may well be regarded as "non-motor" symptoms of essential tremor. Conclusion. Nowadays neurologists are increasingly faced with the problem of differential diagnosis of essential tremor. Despite the fact that everything was very simple and clear on the diagnosis of this disease, in recent years more and more data have appeared in favor of the fact that essential tremor is a heterogeneous disease that manifests not only by tremor. But this is also a disease, which, due to its heterogeneity of pathophysiology, can give great variability in the clinical picture. Keywords: essential tremor, nonmotor symptoms, anxiety, depression, cognitive impairnment, dementia.