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Abstract Parkinsonian tremor (PT) and Essential tremor (ET) exist as upper limb tremors in clinical practice. Notably, their types of trembling share similar presentations and overlapping frequencies. To enhance objectivity and efficiency in the diagnosis of these two diseases, there is a pressing need for more objective tremor classification procedures. This study proposes a novel multimodal fusion network based on a cross-attention mechanism (MFCA-Net) to automate the classification of upper limb tremors between PTs and ETs. To this end, 140 patients with PTs and ETs were recruited, and acceleration and surface electromyography (sEMG) signals were collected from the forearm during tremor episodes. To comprehensively capture the global and local features of input signals, a multiscale convolution in MFCA-Net was designed. Furthermore, the cross-attention mechanism was applied to fuse the features of the two input signals. The results demonstrate that the final classification accuracy exceeded 97.18% when MFCA-Net was used. Compared with the single acceleration signal and single sEMG signal inputs, the recognition accuracies increased by 18.91% and 10.04%, respectively. Therefore, the proposed MFCA-Net in this study serves as an objective and potential tool for assisting clinicians in the diagnosis of PT and ET patients.

Abstract Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1–125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.

Abstract 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.

Objective To identify the pathogenic variants in 110 patients with essential tremor (ET). Methods Clinical data and peripheral blood samples of ET patients were collected from the Department of Neurology of Peking Union Medical College Hospital and then the genomic DNA was extracted. Dynamic mutation detection of NOTCH2NLC was performed in patients with essential tremor by triplet repeat primed PCR(TP-PCR). Since ET is associated with multiple mechanisms of neuro-degeneration, the next generation sequencing (NGS) panel targeting neurodegenerative associating genes were performed to check pathogenic variants in additional genes. Results A total of 110 ET patients and 187 matched control individuals were recruited. The age of onset in the current ET group was (36.30±17.64)years, and 74.8% patients had a family history. No abnormal trinucleotide repeat expansion in NOTCH2NLC was identified. The repeat number of (GGC)n lied within normal ranges between 10-47 (average 18.6±5.4). Variants burden analysis showed association of ET with PLA2G6. Three rare variants in four patients in PLA2G6 were identified with unknown significance. Conclusions Dynamic mutations of NOTCH2NLC are uncommon in ET patients and that suggests need of more researches for further exploring the genetic mechanism of ET.

Background: Tremor is the most common movement disorder, with significant functional and psychosocial consequences. Oral medications have been disappointing or limited by side effects. Surgical techniques are effective but associated with risks and adverse events. Botulinum toxin (BT) represents a promising avenue but there is still no double-blind evidence of efficacy on upper limb function. A systematic review on the effects of BT in upper-limb tremor was conducted. Methods: A systematic search of the literature was conducted up to July 2023, including the keywords “botulinum toxin” and “tremor”. All randomized controlled trials (RCTs) and open-label studies were analyzed. Independent reviewers assessed their methodological quality. Results: There were only eight published RCTs and seven published open-label studies, with relatively small sample sizes. This review suggests that BT is more effective when injections are patient-tailored, with analyses based on clinical judgement or kinematics. Subjective and objective measures frequently improve but transient weakness may occur after injections, especially if wrist or fingers extensors are targeted. A number of studies had methodological limitations. Conclusions: The authors discuss how to optimize tremor assessments and effects of BT injection. Controlled evidence is still lacking but it is suggested that distal “asymmetric” BT injections (targeting flexors/pronators while sparing extensors/supinators) and proximal injections, involving shoulder rotators when indicated, may avoid excessive weakness while optimizing functional benefit.

The Clinical Rating Scale for Tremor (CRST) is commonly used to evaluate essential tremor (ET) during focused ultrasound (FUS) thalamotomy. However, it faces challenges such as the ceiling effect and test–retest variability. This study explored the utility of videographic motion analysis as an evaluation index for ET. Forty-three patients with ET performed postural tremor and line-drawing tasks recorded on video, and the data were analyzed using motion analysis software. The test–retest and inter-rater reliability, correlations with the CRST and tremor scores, and pre/post-FUS treatment comparisons were analyzed. The video motion analysis showed excellent test–retest and inter-rater reliability. In the postural tremor tasks, video parameter amplitude significantly correlated with the CRST and tremor scores. Similarly, for the line-drawing task, video parameter amplitude showed significant correlations with CRST and tremor scores, effectively addressing the ceiling effect. Regarding post-FUS treatment improvements, changes in the CRST and tremor scores were significantly associated with changes in video parameter amplitude. In conclusion, quantitative analysis of the video motion of ET enables precise evaluation of kinematic characteristics and effectively resolves the ceiling effect and test–retest variability. The video motion analysis score accurately reflected the tremor severity and treatment effects, demonstrating its high clinical utility.

Focused ultrasound on the thalamus is employed to relieve tremor in movement disorders. The treatment efficacy is currently assessed by subjective observation of patient tremor during hand movements. The purpose of this study was to create a simple quantitative method to assess tremor based on traditional pen-and-paper spiral drawing that could be employed during treatment and follow-up visits. Image processing was employed to automatically and rapidly clean scanned spiral and line drawings and to isolate the minimal part of the drawing that could provide sufficient data for tremor detection. Sobel edge detection and easily-interpretable statistics of the distribution of edge-angle orientations in the spirals relative to the spiral centres were used as tremor measures. The method was applied to scanned drawings of 122 tremor patients before treatment and in follow-up visits. Discrimination analysis of the tremor measure between drawings in the session before treatment and the follow-up sessions was carried out. The processing yielded correctly cropped and clean spirals. The tremor measure demonstrated consistent tremor reduction in the treated hand drawings in all five follow-up visits during the first year following treatment date in 76 patients from the study cohort. In this study we developed a computational method that rapidly computed tremor severity estimate in an explainable and clinically useful manner from a traditional pen-and-paper spiral drawing. This rapid quantitative and objective tremor assessment can easily be implemented during focused ultrasound treatment and replace the subjective assessment currently employed.

Introduction: Differential diagnoses between essential tremor and Parkinson’s disease is challenging in some individuals, with both disorders sharing similarities. Considering these links, we hypothesized that both conditions have a similar profile for some antioxidant molecules, including 25-hydroxyvitamin D and bilirubin. Methods: We performed a cross-sectional study comparing serum levels of 25-hydroxyvitamin D and bilirubin in 31 ET patients, 38 PD, and 65 controls matched for age. We used the Fahn-Tolosa-Marin scale for the severity of tremors in the ET group. We used Hohen-Yahr and MDS-UPDRS part III scales in the PD group. In addition, we evaluated sociodemographic characteristics, including age, sex, ethnicity, years of study, duration of disease, and use of primidone. Results: We found no differences in serum levels for 25-hydroxyvitamin D or bilirubin subtype levels between the ET and PD groups. We found low levels of indirect bilirubin in the PD group compared to the controls. We did not find differences between ET and controls in all biomarkers of the study. Conclusion: ET and PD patients have similar profiles for 25-hydroxyvitamin D and bilirubin serum levels. The discovery of differences in oxidative stress biomarkers in both conditions, mainly low-cost substances available clinically, can assist in the differential diagnosis and, in the future, prognostication and better therapy management.

Abstract Background Deep brain stimulation has been used since the 1980s for neurological disorders and the USA and Europe have now approved it for Parkinson’s disease, essential tremor, dystonia, and epilepsy. Previous reviews have assessed the effects of deep brain stimulation on different neurological disorders. These reviews all had methodological limitations. Methods This is a protocol for a systematic review based on searches of major medical databases (e.g. MEDLINE, EMBASE, CENTRAL) and clinical trial registries. Two review authors will independently extract data and conduct risk of bias assessment. We will include published and unpublished randomised clinical trial comparing deep brain stimulation versus no intervention, usual care, sham stimulation, medical treatment, or resective surgery for Parkinson’s disease, essential tremor, dystonia, or epilepsy. The effects of deep brain stimulation will be analysed separately for each of the different diagnoses. Primary outcomes will be all-cause mortality, disease-specific symptoms, and serious adverse events. Secondary outcomes will be quality of life, depressive symptoms, executive functioning, level of functioning, and non-serious adverse events. Data will be analysed using fixed-effect and random-effects meta-analyses and Trial Sequential Analysis. Risk of bias will be assessed with the Cochrane Risk of Bias tool—version 2, an eight-step procedure to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Discussion Deep brain stimulation is increasingly being used for different neurological diseases, and the effects are unclear based on previous evidence. There is a need for a comprehensive systematic review of the current evidence. This review will provide the necessary background for weighing the benefits against the harms when assessing deep brain stimulation as intervention for individual neurological disorders. Systematic review registration PROSPERO 306,556.

Background: Essential tremor is the most common movement disorder. İn this disease, which is characterized by tremor that increases with action and passes at rest, different accompanying symptoms can also be seen. Objective: The purpose of this study was to investigate attention deficit hyperactivity symptoms in adults with ET. Methods: Fifty six essential tremor patients and 56 controls were included in the study. Patients were recruited from outpatient clinic at Kirikkale University Medicine Faculty. An informed consent form was signed by each patient after detailed information. Institutional ethics committee approval was obtained. Patients’ characteristics such as education level, gender, age and disease duration were recorded. Symptoms of ADHD in patients and controls were determined by using the Adult Report Deficit / Hyperactivity Disorder Self Report Scale. Short Form-36 and Hospital Anxiety and Depression Scale were also performed. Essential tremor severity was determined by using the Whiget essential tremor scale. Results: Essential tremor patients had significantly higher rate of Adult Attention Disorder Self-Report Scale Deficit/Hyperactivity scores compared to controls. Scores of Adult Attention Deficit/Hyperactivity Disorder Self-Report Scale were associated with depression and anxiety scores and physical and mental component scores of Short Form-36 in bivariate analyses. There was a positive correlation between tremor severity and ASRS scores( ASRS A scores= 17,3±5,5, p=0,032, ASRS B scores= 27,7±6,7,p=0,043, ASRS T scores= 45±12,2, p=0,017) however there was no significant statistical relationship between the duration of disease and ASRS scores. Conclusion: This study showed that ADHD symptoms can be observed in adult essential tremor patients and this may be associated with increased psychosocial morbidity and lowered quality of life in ET patients.

Objective: Essential tremor (ET) is the most common movement disorder in the general population. Approximately, 90% of patients have upper extremity tremors. Patients with ET generally have a problem in motor control and some have serious problems in eating, drinking, writing, and other activities of daily living (ADL). Thus, ET may cause disability and self-care problems in their lives. Recent studies showed that ADL was impaired in 73% of patients. This study aimed to determine the effects of disability and self-care agency on ADL in patients with ET. Materials and Methods: This study includes 50 patients with ET. Brief disability questionnaire, self-care agency scale, Katz index of independence in ADL, and Fahn Tolasa Marin tremor scale were evaluated in the patients. Results: Among all patients, 58% (n=29) were female. The mean age of patients was 62.1 years. In addition, 72% of patients had hand tremors. More than 52% of patients had stage 2 diseases according to the Fahn Tolasa Marin tremor scale. Disability was detected in 62% of patients. In general, the mean disability scores were significantly higher in female patients compared to males. A positive correlation was found between disability and ADL. Moreover, a significant relationship between self-care agency and ADL was found. Conclusion: Our study shows that disability increases as the stage of the disease progress. In addition, as the disability due to ET becomes more severe, the selfcare agency of patients decreases. Moreover, their dependence on ADL has been observed.

Summary: Background: Essential tremor (ET), one of the most common neurological disorders, has a phenotypically heterogeneous presentation characterized by bilateral kinetic tremor of the arms and, in some patients, tremor involving other body regions (e.g., head, voice). Genetic studies suggest that ET is genetically heterogeneous. Methods: We analyzed whole genome sequence data (WGS) generated on 104 multi-generational white families with European ancestry affected by ET. Genome-wide parametric linkage and association scans were analyzed using adjusted logistic regression models through the application of the Pseudomarker software. To investigate the additional contribution of rare variants in familial ET, we also performed an aggregate variant non-parametric linkage (NPL) analysis using the collapsed haplotype method implemented in CHP-NPL software. Findings: Parametric linkage analysis of common variants identified several loci with significant evidence of linkage (HLOD ≥3.6). Among the gene regions within the strongest ET linkage peaks were BTC (4q13.3, HLOD=4.53), N6AMT1 (21q21.3, HLOD=4.31), PCDH9 (13q21.32, HLOD=4.21), EYA1 (8q13.3, HLOD=4.04), RBFOX1 (16p13.3, HLOD=4.02), MAPT (17q21.31, HLOD=3.99) and SCARB2 (4q21.1, HLOD=3.65). CHP-NPL analysis identified fifteen additional genes with evidence of significant linkage (LOD ≥3.8). These genes include TUBB2A, VPS33B, STEAP1B, SPINK5, ZRANB1, TBC1D3C, PDPR, NPY4R, ETS2, ZNF736, SPATA21, ARL17A, PZP, BLK and CCDC94. In one ET family contributing to the linkage peak on chromosome 16p13.3, we identified a likely pathogenic heterozygous canonical splice acceptor variant in exon 2 of RBFOX1 (ENST00000547372; c.4-2A>G), that co-segregated with the ET phenotype in the family. Interpretation: Linkage and association analyses of WGS identified several novel ET candidate genes, which are implicated in four major pathways that include 1) the epidermal growth factor receptor-phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha-AKT serine/threonine kinase 1 (EGFR-PI3K-AKT) and Mitogen-activated protein Kinase 1 (ERK) pathways, 2) Reactive oxygen species (ROS) and DNA repair, 3) gamma-aminobutyric acid-ergic (GABAergic) system and 4) RNA binding and regulation of RNA processes. Our study provides evidence for a possible overlap in the genetic architecture of ET, neurological disease, cancer and aging. The genes and pathways identified can be prioritized in future genetic and functional studies. Funding: National Institutes of Health, NINDS, NS073872 (USA) and NIA AG058131(USA).

Summary: Background: Tremors are frequent and disabling in people with multiple sclerosis (MS). Characteristic tremor frequencies in MS have a broad distribution range (1–10 Hz), which confounds the diagnostic from other forms of tremors. In this study, we propose a classification method for distinguishing MS tremors from other forms of cerebellar tremors. Methods: Electromyogram (EMG), accelerometer and clinical data were obtained from a total of 120 [40 MS, 41 essential tremor (ET) and 39 Parkinson's disease (PD)] subjects. The proposed method - Soft Decision Wavelet Decomposition (SDWD) - was used to compute power spectral densities and receiver operating characteristic (ROC) analysis was performed for the automatic classification of the tremors. Association between the spectral features and clinical features (FTM - Fahn-Tolosa-Marin scale, UPDRS - Unified Parkinson's Disease Rating Scale), was assessed using a support vector regression (SVR) model. Findings: Our developed analytical framework achieved an accuracy of up to 91.67% using accelerometer data and up to 91.60% using EMG signals for the differentiation of MS tremors and the tremors from ET and PD. In addition, SVR further revealed strong significant correlations between the selected discriminators and the clinical scores. Interpretation: The proposed method, with high classification accuracy and strong correlations of these features to clinical outcomes, has clearly demonstrated the potential to complement the existing tremor-diagnostic approach in MS patients. Funding: This work was supported by the German Research Foundation (DFG): SFB-TR-128 (to SG, MM), MU 4354/1-1(to MM) and the Boehringer Ingelheim Fonds BIF-03 (to SG, MM).

Rationale for choosing. An increase in physiological tremor (Tr) in emotionally saturated situations is reflected not only in fiction, but also in scientific literature. In other words, tremors and emotional responses are interconnected. Purpose. To investigate the reflection of individual-typological properties in a tremorogram using V. M. Rusalov’s mathematical modeling. Material and methods. Tr was recorded using a linear transducer. Tr was recorded under postural load (arms extended forward). The sensor was alternately placed on the outstretched right and left arms in front of oneself, under conditions of “eyes open” (operative rest). The analysis of the tremorogram (TrG) files was carried out after the end of the study using the "Analist - 2" software according to the half - period analysis algorithm. To study the individual psychological characteristics of the personality, we used the method of determining the properties of the temperament by V.M. Rusalov. Each of the many indicators of Rusalov’s test selected in the analysis was considered as a target feature (Y-s), and the amplitudes and frequencies of TrG were considered as influencing variables (sets of X - s) and multiple linear regression equations of the form were built: The parameters of the amplitude and frequency of EEG rhythms were used as Xs. Own research. In multiple regression analysis of the influence of TrG indices of the right hand on the indices of Rusalov’s test, 12 statistically significant regression coefficients were determined, and 11 statistically significant regression coefficients for the left hand. After obtaining the diagnostic equations of multiple linear regression, describing the influence of TrG indicators on the indicators of Rusalov’s test, an attempt was made, using these equations, to obtain the indicators of Rusalov’s test, using the tremor indicators. On average, the% discrepancy between the determined and predicted indicators was 97.42% for the right hand, and 101.98 for the left. Conclusions. 1. With the use of diagnostic equation, it was possible to predict the indicators of psychological testing according to Rusalov’s test by the indicators of tremor of the right and left hands.2. Influence of Rusalov’s test indicators on TrG indicators were less in modulus than the influence of TrG indicators on the indicators of Rusalov’s test, i.e. did not participate in the control of the mechanisms of TrG generation.3. The results obtained indicate that tremor indicators contain information about the subject-activity and communicative aspects of temperament according to V. M. Rusalov.

The pooled incidences of treatment-emergent adverse events (TEAEs) were examined by indication using the integrated clinical database of Merz-sponsored, placebo-controlled, or repeat-dose studies of incobotulinumtoxinA in adults with cervical dystonia, blepharospasm, limb spasticity, sialorrhea, or essential tremor of the upper limb. Overall incidences of TEAEs, serious TEAEs, TEAEs leading to discontinuation, fatal TEAEs, TEAEs of special interest (TEAESIs; indicating possible toxin spread), and treatment-related (TR) events were determined for incobotulinumtoxinA and placebo after a single injection and for repeated dose cycles of incobotulinumtoxinA. The most frequent events after a single dose of incobotulinumtoxinA are summarized. After a single cycle, incidences of overall TEAEs were similar between incobotulinumtoxinA and the placebo in most indications, although between-indication differences were observed. Few TEAEs led to incobotulinumtoxinA discontinuation; there were no fatal TEAEs with incobotulinumtoxinA. In general, repeated cycles did not increase the incidence of any event. The most frequent TR-TEAEs were indication-dependent, including dysphagia for indications affecting the head or neck. The TR-TEAESIs across all indications were most commonly muscular weakness, dysphagia and dry mouth. Overall, the results of this pooled analysis support and extend the favorable safety and tolerability profile of incobotulinumtoxinA for the treatment of adult neurological disorders established by individual clinical studies.

Programming in deep brain stimulation (DBS) is often a labour-intensive process. Although automatic closed-loop stimulation has recently been receiving considerable attention, it is still far from clinical settings. Testing in-loop stimulation in a clinical setting is extremely challenging due to manual programming and the lack of synchronisation between stimulation and monitoring devices. In this work, we present a simple rulebased expert system to test feedback-controlled DBS in a clinical setting. The new application operates in closed-loop with the physician as acting person and real-time feedback from an accelerometer. Patients with movement disorders such as in essential tremor announce an individually acceptable level of tremor as a boundary condition for control. As a proof-of-concept, the expert system provides continuous recommendations of stimulation parameters and guides the physician to increase or decrease DBS amplitude by capturing tremor acceleration power on the patients’ forearms. The introduced application considers the technical and practical aspects in a clinical setting. Data obtained from test subjects provide insight into tremor dynamics. We demonstrate the clinical applicability of the rule-based control system for future research focusing on tremor dynamics and inloop stimulation. Finally, a telemetry streaming system could provide the interface for the application of automatic tremor control without the physician as acting person.

In the clinical picture of essential tremor (ET), in addition to tremulous hyperkinesis, the importance of non-motor manifestations has recently been discussed. Despite their high occurrence, in most cases these manifestations remain unverified. The purpose of this study was to assess the incidence of non-motor symptoms (NMS) in patients with ET. The study included 3 groups comparable by sex and age. Group 1 (the main group) consisted of 53 patients with ET; Group 2 consisted of 57 patients with Parkinson's disease (PD); Group 3 consisted of 111 individuals without ET or PD, and without burdened heredity for extrapyramidal diseases. All subjects filled out the NMSQuest scale, which contains 30 questions for various groups of NMS. The analysis of NMS using the NMSQues scale in the three study groups showed a similarity between ET plus and PD in non-motor manifestations.

Background Essential tremor (ET) is the most common movement disorder. Propranolol is a first-line medication for ET. We aimed to evaluate the effect of propranolol on the expression of poly (ADP-ribose) polymerase 1 (PARP1) and DNA polymerase beta (POLB) genes, which are known to be related to neurodegenerative diseases, in patients with ET. Methods Thirty-five healthy volunteers and thirty-five patients followed up with essential tremors were included in a non-randomized control experimental study. Expressions of PARP1 and POLB genes were compared between the control group and the patient group. In addition, pre- and post-treatment gene expression levels and Fahn-Tolosa-Marin tremor scale values of the patient group were compared after 8 weeks of propranolol treatment. The Wilcoxon rank and Mann Whitney U tests were used to analyze the data. Results At baseline, PARP1 expression was significantly lower in the ET group than in the control group. (p

Voice tremor is a common, yet debilitating symptom for patients suffering from a number of tremor-associated disorders. The key to targeting effective treatments for voice tremor requires a fundamental understanding of the pathophysiology that underpins the tremor mechanism and accurate identification of the disease in affected patients. An updated review of the literature detailing the current understanding of voice tremor (with or without essential tremor), its accurate diagnosis and targeted treatment options was conducted, with a specific focus on the role of botulinum neurotoxin. Judicious patient selection, following detailed characterisation of voice tremor qualities, is essential to optimising treatment outcomes for botulinum neurotoxin therapy, as well as other targeted therapies. Further focused investigation is required to characterise the response to targeted treatment in voice tremor patients and to guide the development of innovative treatment options.

Abstract Essential tremor (ET) is one of the most common movement disorders. However, there are currently no accepted biomarkers for ET. This report suggested that concentration of plasma glutamic acid, aspartic acid, and taurine could be biomarkers for ET.

Despite the developed criteria of essential tremor (ET) and Parkinson’s disease (PD), clinical practice shows a high percentage of misdiagnoses, especially in the early stages of the disease and during the patient’s initial contact with a neurologist. In addition, the same patient may have signs of ET and PD at the same time. For a correct diagnosis, a detailed clinical examination is necessary. The specific characteristics of tremor (frequency, amplitude, type, involvement of specific parts of the body), history, associated neurological signs, and concomitant non-motor symptoms help to recognize and distinguish these two diseases. In order to exclude the possible negative effect of concomitant medications on tremor, it is necessary to find out about the medication history. The article offers an algorithm of survey and inspection, as well as the interpretation of the data obtained. In diagnostically complicated cases, «trial» therapy is carried out. Additional information for differential diagnosis can be provided by the results of instrumental methods of investigation of transcranial sonography of black substance and single-photon emission computed tomography (DaTSCAN).

The technique of deep brain stimulation is used to treat patients with various diseases of the central nervous system who are not amenable to conservative therapy, while open interventions in them are associated with a high risk of complications. In the review, we evaluate the efficiency of the deep stimulation of different regions of the brain in some pharmacoresistant forms of diseases.

Background: Botulinum toxin type A (BoNT-A) therapy for upper-limb tremor has emerged as a promising option. However, it is unclear in real-world practices whether a technology-guided approach can compare with expert clinical assessments (including surface anatomy and palpation) for improving outcomes. This retrospective study aims to review our clinical outcomes of treating essential tremor (ET) and Parkinson’s disease (PD) tremor using either clinical- or kinematic-based injection pattern determination methods. Methods: 68 ET and 45 PD patients received at least one injection for their upper-limb tremor (unilateral or bilateral) in the last 7 years. Demographics of patients and BoNT-A injections were collected. A Mann–Whitney U statistical test was used to compare outcome measures between ET and PD cohorts. Results: Mean age (72 ± 9 years), number of injections (5), years receiving therapy (~2 years), clinic- (~57%) or kinematic-based patterns, and self-paying (52%) were similar between both cohorts. BoNT-A as a monotherapy in both upper limbs was received in more ET than PD patients. Double reconstitution of Xeomin® in the wrist flexors/extensors, supinator, biceps, and triceps were most injected. Discontinuation due to no benefit/weakness was not dependent on the injection pattern determination approach. Conclusions: Kinematic-based BoNT-A injections produced similar treatment outcomes to injections based on the clinical expertise of the expert injector. This suggests that kinematics could be used by a non-expert to attain equivalent efficacy potentially improving access to this treatment.

Background Essential tremor (ET) is the most common disease among movement disorders. Genes such as essential tremor 1-4 (ETM 1-4), HS1-binding protein-3 (HS1BP3), dopamine receptor D3 (DRD3), leucine-rich repeat and Ig domain containing 1 (LINGO1), glial high affinity glutamate transporter member 2 (SLC1A2), FUS, high temperature requirement A2 (HTRA2) and TENM4 had been shown to be responsible for the genetic inheritance of the disease. The aim of the present study was to investigate the effect of propranolol on the expression of DRD3, SLC1A2, and HTRA2 genes in patients with ET. Methods A study of non-randomized experimental design was conducted involving 76 subjects. They were divided into two groups: 38 patients with ET in the patient group (Group 1) and 38 healthy people in the control group (Group 2). DRD3, SLC1A2 and HTRA2 gene expressions were assessed before and after 8 weeks of propranolol treatment. Fahn-Tolosa-Marin tremor scale results were compared before and after propranolol administration. Kruskal Wallis test was used to determine differences in gene expressions between the groups. Results D3 dopamine receptor and SLC1A2 gene expression in the patient group appeared to be lower than in the control group (p

Objective: Essential tremor (ET) is the most common cause of tremor. We know that this disease, which was presumed to be monosymptomatic until recently, may be accompanied by motor findings and a series of non-motor findings other than action tremor. Alexithymia can be defined as not being able to name emotions, express emotions, distinguish emotions from each other, or living without being aware of one’s own emotions. The aim of our study was to evaluate alexithymia in patients with ET. Materials and Methods: Forty-four patients with ET (mean age=38.22±18.05 years) and 46 control subjects (mean age=37.17±10.68 years) were included in the study. The Fahn-Tolosa-Marin Tremor Rating Scale was used for the patient group and the Toronto Alexithymia Scale (TAS), Beck Depression Inventory and Beck Anxiety Inventory were applied to both groups. Results: The mean TAS was 49.16±8.94 in the patient group and 42.34±6.27 in the control group (p

Objective: Although the effectiveness of postural balance training on balance and gait impairment has been proven as an effective treatment approach in several patient and healthy populations, its effectiveness in patients with essential tremor (ET) is yet unknown. The aim was to examine the effects of postural balance training program on balance and gait performance, and health-related quality of life in patients with ET. Materials and Methods: This uncontrolled clinical study included patients with ET. The outcome measures were the Postural Stability Test, Limits of Stability Test, Fall Risk Test, Activities-Specific Balance Confidence scale, Dynamic Gait Index, and Short Form-36. The assessments were performed before and after the training program. The participants underwent an 8-week balance training designed to improve their ability to integrate multisensory inputs and postural control using a computerized balance assessment and training device. Results: In total, 24 patients with ET participated in the study. The compliance rate was 87.5%. There were significant improvements in all outcome measures of balance and gait performance, balance confidence, fall risk, and health-related quality of life (except the mental component, p>0.05) between baseline and 8 weeks (p

There are many reports suggesting an important role of genetic factors in the etiopathogenesis of essential tremor (ET), encouraging continuing the research for possible genetic markers. Linkage studies in families with ET have identified 4 genes/loci for familial ET, although the responsible gene(s) have not been identified. Genome-wide association studies (GWAS) described several variants in LINGO1, SLC1A2, STK32B, PPARGC1A, and CTNNA3, related with ET, but none of them have been confirmed in replication studies. In addition, the case-control association studies performed for candidate variants have not convincingly linked any gene with the risk for ET. Exome studies described the association of several genes with familial ET (FUS, HTRA2, TENM4, SORT1, SCN11A, NOTCH2NLC, NOS3, KCNS2, HAPLN4, USP46, CACNA1G, SLIT3, CCDC183, MMP10, and GPR151), but they were found only in singular families and, again, not found in other families or other populations, suggesting that some can be private polymorphisms. The search for responsible genes for ET is still ongoing.

Objective: In multiple sclerosis (MS); memory, attention, information processing speed, and executive function deficits associated with cortical demyelination and atrophy can be seen in the early phases. In essential tremor (ET) cognitive impairment associated with cerebral-thalamocortical pathway dysfunction, which is characterized by visuospatial functions, verbal memory, and executive functions were seen. We aimed to evaluate cognitive impairment in patients with MS and ET, and to compare the features of impairment. Materials and Methods: Thirty patients ET (mean age 27.7±6.8 years), 30 patients with MS (mean age 32.4±6.6 years) and 20 healthy controls (mean age 28.81±7.3 years) were recruited for the study. For assessing cognitive impairment, the Montreal Cognitive Assessment (MoCA) test was applied to all participants. For grading the disease, the Fahn-Tolosa-Marin Tremor Rating Scale was used in the ET group, and the Expanded Disability Status Scale was used in the MS group. Results: The total MoCA mean scores in patients with MS was 22.4±4.34, 25.8±2.7 in patients with ET, and 28.2±1.8 in controls. When we compared the patients with the controls, the patients’ mean score was lower than in the controls. Cognitive impairment in patients with MS was more apparent than in patients with ET. Naming, attention, language, and delayed recall subgroups in patients with MS were more affected than in patients with ET. Conclusion: In this present study, we determined cognitive impairment can be seen in both group of patients, and MS can cause more prominent deficit than ET. In addition, our study confirms that cognitive impairment in MS and ET can be detected using the MoCA test.

Background: Essential tremor is one of the most prevalent extrapyramidal disorders, while treatment efficacy in such patients remains low. Clinical polymorphism of essential tremor requires a differentiated treatment approach, that should be implemented with consideration of objective tremor parameters. Aim: To study efficacy of treatment of essential tremor based on tremorography. Materials and methods: We followed up 85 patients with essential tremor (mean age, 69.05±1.2 years) who were treated with anticonvulsants as monotherapy (primidone or topiramate), or with combination treatment with non-selective beta-blockers (propranolol), anxiolytics (hydroxizine, etifoxine) and aminophenylbutyric acid. During the treatment, we assessed changes in functional status by Fahn-Tolosa-Marin Tremor Severity Scale and by tremorography. Results: Under treatment with primidone, there was a decrease in global tremor assessment of postural tremor (p=0.036) and of action tremor (p=0.001). During treatment with topiramate, there was a decrease in global tremor assessment in all tests performed (p

Essential tremor (ET) and Parkinson’s disease (PD) are among the most common adult-onset tremor disorders. Clinical and pathological studies suggest that misdiagnosis of PD for ET, and vice versa, occur in anywhere from 15% to 35% of cases. Complex diagnostic procedures, such as dopamine transporter imaging, can be powerful diagnostic aids but are lengthy and expensive procedures that are not widely available. Preliminary studies suggest that monitoring of tremor characteristics with consumer grade accelerometer devices could be a more accessible approach to the discrimination of PD from ET, but these studies have been performed in well-controlled clinical settings requiring multiple maneuvers and oversight from clinical or research staff, and thus may not be representative of at-home monitoring in the community setting. Therefore, we set out to determine whether discrimination of PD vs. ET diagnosis could be achieved by monitoring research subject movements at home using consumer grade devices, and whether discrimination could be improved with the addition of genetic profiling of the type that is readily available through direct-to-consumer genetic testing services. Forty subjects with PD and 27 patients with ET were genetically profiled and had their movements characterized three-times a day for two weeks through a simple procedure meant to induce rest tremors. We found that tremor characteristics could be used to predict diagnosis status (sensitivity = 76%, specificity = 65%, area under the curve (AUC) = 0.75), but that the addition of genetic risk information, via a PD polygenic risk score, did not improve discriminatory power (sensitivity = 80%, specificity = 65%, AUC = 0.73).