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© 2021 International Parkinson and Movement Disorder Society, The landscape of genetic forms of Parkinson's diseases (PD) has grown exponentially in recent years. Today, around 10% of PD cases are estimated to be of genetic etiology. However, the link between parkinsonism or tremor and chromosome disorders, both numerical and structural, has been neglected. We reviewed the occurrence and characteristics of parkinsonism and tremor syndromes in patients with chromosomic disorders. We searched PubMed for articles published until December 2018, using the non-MESH terms "Chromosomopathy," "karyotype," "chromosome," "aneuploidy," "deletion," "inversion," "insertion," "duplication," and "Parkinson," "Parkinsonism," "Tremor," and "Parkinsonian disorder." We restricted the search to human studies and selected articles for further analysis after abstract review. Tremor syndromes in which patients had another possible clinical reason for syndromes were excluded, as well as tremor syndromes associated with point mutations, imprinting syndromes, and patients presenting with other hyperkinetic disorders. Fifty-four articles were reviewed. Aneuploidies of sex chromosomes were the most common chromosomopathy. These patients more commonly exhibited postural and kinetic tremor, often meeting the description of essential tremor. In structural chromosomopathies, the most frequent association was PD and 22q11.2 deletion syndrome, but we found case reports and case series of several additional deletion and duplication syndromes.

Objective Although Essential Tremor is one of the most common movement disorders, we do not currently know which muscles are most responsible for tremor. Determining this requires multiple steps, one of which is characterizing the distribution of tremor among the degrees of freedom (DOF) of the upper limb. Methods Upper-limb motion was recorded while 22 subjects with ET performed postural and kinetic tasks involving a variety of limb configurations. We calculated the mean distribution of tremor among the seven DOF from the shoulder to the wrist, as well as the effect of limb configuration, repetition, and subject characteristics (sex, tremor onset, duration, and severity) on the distribution. Results On average, kinetic tremor was greatest in forearm pronation-supination and wrist flexion–extension, intermediate in shoulder internal-external rotation and wrist radial-ulnar deviation and then shoulder flexion–extension and elbow flexion–extension, and least in shoulder abduction–adduction. The average distribution of postural tremor was similar except for forearm pronation-supination, which played a smaller role than in kinetic tremor. Limb configuration and subject characteristics did significantly affect tremor, but practically only in forearm pronation-supination and wrist flexion–extension. There were no significant differences between repetitions, indicating that the distribution was consistent over the duration of the experiment. Conclusions This paper presents a thorough characterization of tremor distribution from the shoulder to the wrist. Significance Understanding which DOF exhibit the most tremor may lead to more targeted peripheral tremor suppression.

Background Fragile X-associated Tremor/Ataxia Syndrome (FXTAS) is a rare, late-onset neurodegenerative disorder characterized by tremor and cerebellar gait ataxia, affecting premutation carriers (PMC) of CGG expansions (range, 55-200) in the fragile X mental retardation 1 (FMR1) gene. Discovery of early predictors for FXTAS and quantitative characterization of motor deficits are critical for identifying disease onset, monitoring disease progression, and determining efficacy of interventions. Methods A total of 39 PMC with FXTAS, 20 PMC without FXTAS, and 27 healthy controls performed a series of upper extremity (UE) motor tasks assessing tremor, bradykinesia, and rapid alternating movements that were quantified using an inertial-based sensor system (Kinesia One; Great Lakes NeuroTechnologies, Cleveland, OH, USA). Sub-scores from the clinician-rated FXTAS Rating Scale were correlated with the severity scores generated by the sensor system to determine its validity in FXTAS. Results PMC with FXTAS had significantly worse postural and kinetic tremor compared with PMC without FXTAS (P = 0.02, 0.03) and controls (P = 0.001, 0.0001), respectively, and slower finger tap (P = 0.001), hand movement (P = 0.0001), and rapid alternating movement speed (P = 0.003) and amplitude (P = 0.04) than controls. PMC without FXTAS had significantly worse right finger tap (P = 0.004), hand movement (P = 0.01), and rapid alternating movement speed (P = 0.003) and amplitude (P = 0.02) than controls. FXTAS Rating Scale subscores significantly correlated with all tremorography scores except for finger taps and left rapid alternating movement. Conclusions These findings support the use of inertial sensor quantification systems as promising measures for preclinical FXTAS symptom detection in PMC, characterization of the natural history of FXTAS, assessment of medication responses, and outcome assessment in clinical trials.

Background and purpose Essential tremor (ET) is a movement disorder primarily characterized by upper limb postural and kinetic tremor. Although still under-investigated, bradykinesia may be part of the phenotypic spectrum of ET. The aim was to evaluate bradykinesia features in ET through clinical examination and kinematic analysis of repetitive finger movements. Data collected in ET patients were compared with those recorded in Parkinson's disease patients and healthy controls. Methods Overall, 258 subjects participated in the study (90 ET patients, 84 Parkinson's disease patients and 84 healthy controls). Repetitive finger tapping was kinematically recorded using a motion analysis system. Movement velocity, amplitude and decrement (sequence effect) were measured. The three groups were first compared by one-way analysis of variance. A cluster analysis was also performed to better address the data variability observed in ET patients. Possible relationships between kinematic and clinical data were assessed in ET patients. Results Essential tremor patients were slower than healthy controls. Movement slowness in ET did not correlate with postural or kinetic tremor severity. It was also found that movement slowness in ET was not associated with a sequence effect, which instead is a common feature in Parkinson's disease. Cluster analysis showed that a proportion of ET patients may have movement abnormalities similar to those observed in Parkinson's disease. Conclusions Movement slowness without sequence effect is a common feature in ET patients. The present findings are relevant when interpreted in the context of the new tremor classification system and in the development of a more accurate bradykinesia definition.

Essential tremor (ET) is the most common tremor disorder globally and is characterized by kinetic tremor of the upper limbs, although other clinical features can also occur. Postmortem studies are a particularly important avenue for advancing our understanding of the pathogenesis of ET; however, until recently, the number of such studies has been limited. Several recent postmortem studies have made important contributions to our understanding of the pathological changes that take place in ET. These studies identified abnormalities in the cerebellum, which primarily affected Purkinje cells (PCs), basket cells and climbing fibres, in individuals with ET. We suggest that some of these pathological changes (for example, focal PC axonal swellings, swellings in and regression of the PC dendritic arbor and PC death) are likely to be primary and degenerative. By contrast, other changes, such as an increase in PC recurrent axonal collateral formation and hypertrophy of GABAergic basket cell axonal processes, could be compensatory responses to restore cerebellar GABAergic tone and cerebellar cortical inhibitory efficacy. Such compensatory responses are likely to be insufficient, enabling the disease to progress. Here, we review the results of recent postmortem studies of ET and attempt to place these findings into an anatomical–physiological disease model. In this Review, the authors discuss the results of recent postmortem studies of essential tremor and propose a disease model that involves both primary neurodegenerative changes and compensatory responses.

The spiral drawing task is a representative clinical test used to assess essential tremor. Many clinicians have used spirography to assess through visual rating of the drawings. We quantitatively investigated the clinical characteristics of action tremors during spiral drawing tasks using 3-axis gyro sensors. Eighteen essential tremor patients with sensors attached to their forefinger, dorsum of the hand, and forearm participated in a spiral drawing test. As quantitative variables, the average speed, maximum frequency and maximum power were derived from the gyro sensor signals. The average speed and maximum power were also logarithmically transformed. Two-way repeated measures analysis of variance (ANOVA) with tremor direction and joint (attachment location) as independent factors was performed to evaluate the main and interactive effects of direction and joint. Also, Spearman’s correlation analysis was performed to evaluate the relationship between the quantitative variables and visual rating scores. The average speed showed a significant main effect of direction ([Formula: see text]). Logarithmic variables showed interactive effects ([Formula: see text]) as well as main effects ([Formula: see text]). The interactive effects were attributed to no significant difference among the joints particularly in the roll direction ([Formula: see text]). The logarithmic variables of roll direction were significantly greater than that of the other directions ([Formula: see text]). Also, the quantitative variables were moderately correlated with visual rating scores ([Formula: see text], [Formula: see text]). These results indicate that kinetic tremor during spiral drawing mainly appears in the roll direction and may contribute to the determination of sensor location and direction for continuous monitoring of patients with essential tremor.

Purpose of review Tremor is a common neurological symptom with a plethora of potential etiologies. Apart from physiological tremor, the vast majority of tremor syndromes are linked to a pacemaker in the central nervous system (CNS) or, less common, in the peripheral nervous system. Myogenic tremor is a novel tremor entity, first reported in 2019 and believed to originate in the muscle itself. In this review, we describe the clinical properties of myogenic tremor and discuss its presumed pathogenesis on the basis of all of the patient cases published so far. Recent findings Myogenic tremor manifests itself as a high frequency, postural, and kinetic tremor with onset in infancy. To date, only myopathies affecting the contractile elements, in particular myosin and a myosin-associated protein, have been recognized to feature myogenic tremor. The generator of the tremor is believed to be located in the sarcomere, with propagation and amplification of sarcomeric oscillatory activity through CNS reflex loops, similar to neuropathic tremor. Summary True myogenic tremor must be distinguished from centrally mediated tremor due to myopathies with central nervous system involvement, i.e., mitochondrial myopathies or myotonic dystrophies. The presence of myogenic tremor strongly points toward a sarcomere-associated mutation and may thus be a valuable clinical tool for the differential diagnosis of myopathies.

Lesions in the Guillain–Mollaret (G–M) triangle frequently cause various types of tremors or tremor-like movements. Nevertheless, we know relatively little about their generation mechanisms. The deep cerebellar nuclei (DCN), which is a primary node of the triangle, has two main output paths: the primary excitatory path to the thalamus, the red nucleus (RN), and other brain stem nuclei, and the secondary inhibitory path to the inferior olive (IO). The inhibitory path contributes to the dentato-olivo-cerebellar loop (the short loop), while the excitatory path contributes to the cerebrocerebellar loop (the long loop). We propose a novel hypothesis: each loop contributes to physiologically distinct type of tremors or tremor-like movements. One type of irregular tremor-like movement is caused by a lesion in the cerebrocerebellar loop, which includes the primary path. A lesion in this loop affects the cerebellar forward model and deteriorates its accuracy of prediction and compensation of the feedback delay, resulting in irregular instability of voluntary motor control, i.e., cerebellar ataxia (CA). Therefore, this type of tremor, such as kinetic tremor, is usually associated with other symptoms of CA such as dysmetria. We call this type of tremor forward model-related tremor. The second type of regular tremor appears to be correlated with synchronized oscillation of IO neurons due, at least in animal models, to reduced degrees of freedom in IO activities. The regular burst activity of IO neurons is precisely transmitted along the cerebellocerebral path to the motor cortex before inducing rhythmical reciprocal activities of agonists and antagonists, i.e., tremor. We call this type of tremor IO-oscillation-related tremor. Although this type of regular tremor does not necessarily accompany ataxia, the aberrant IO activities (i.e., aberrant CS activities) may induce secondary maladaptation of cerebellar forward models through aberrant patterns of long-term depression (LTD) and/or long-term potentiation (LTP) of the cerebellar circuitry. Although our hypothesis does not cover all tremors or tremor-like movement disorders, our approach integrates the latest theories of cerebellar physiology and provides explanations how various lesions in or around the G–M triangle results in tremors or tremor-like movements. We propose that tremor results from errors in predictions carried out by the cerebellar circuitry.

Background: Essential tremor (ET) is one of the most common movement disorders of adults, characterized by postural and kinetic tremor. With drug treatment only partially efficient, new treatments are being developed. Objectives: The goal of this study was to demonstrate the feasibility of non-thermal focused-ultrasound (FUS) to induce tremor-suppression in an ET rat model. Methods: Harmaline-induced tremor rats were treated with FUS along the inferior olivary (IO) system. EMG was recorded continuously during treatment in order to quantify FUS-induced tremor suppression. T2-weighted MRI was performed immediately following treatment and periodically thereafter. Results: FUS treatment at an intensity of 27.2 W/cm2 (Isppa) induced significant reduction of tremor in 12 out of 13 ET rats. Tremor frequency was reduced from 6.2 ± 2.8 to 2 ± 1 Hz, p

Objective: Approximately 25% of individualsliving with parkinsonian tremor do not respond to traditional treatments. Wearable tremor suppression devices (WTSD) provide an alternative approach, however, tremor in the fingers has not been given as much attention as tremor in the elbow and the wrist. Therefore, the objective of this study is to design a wearable tremor suppression glove that can suppress tremor simultaneously, but independently, in multiple hand joints without restricting the user's voluntary motion. Methods: A WTSD was designed for managing tremor in the index finger metacarpophalangeal (MCP) joint, thumb MCP joint, and the wrist. The prototype was tested and assessed on a participant living with parkinsonian tremor. Results: The experimental evaluation showed an overall suppression of 73.1%, 80.7%, and 85.5% in resting tremor, 70.2%, 79.5%, and 81% in postural tremor, and 60.0%, 58.7%, and 65.0% in kinetic tremor in the index finger MCP joint, the thumb MCP joint, and the wrist, respectively. Conclusion: This first assessment of a WTSD for people living with Parkinson's disease provides confirmation of the feasibility of the approach. The next step requires a comprehensive validation on a broader population in order to evaluate the performance of the WTSD. Significance: This study demonstrates the feasibility of using a WTSD to manage hand and finger tremor. The device enriches the field of upper-limb tremor management, as the first WTSD for multiple joints of the hand.

A 73-year-old right-handed man with hypertension, hypercholesterolemia, renal insufficiency, and cyclothymic disorder presented with 1 year of insidious onset tremor in his right hand when carrying his briefcase. Psychotropic drugs included bupropion and lamotrigine. He was neurologically intact except for a very low amplitude bilateral kinetic tremor (L > R) and a much larger amplitude right hand task-specific tremor (video 1) characterized by EMG (figure).

Fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in carriers of fragile X mental retardation 1 (FMR1) X-linked small CGG expansion (gray zone [GZ] and premutation [PM]) alleles, containing 41–200 repeats. Major features comprise kinetic tremor, gait ataxia, cognitive decline and cerebellar peduncular white matter lesions, but atypical/incomplete FXTAS may occur. We explored the possibility of polygenic effects modifying the FXTAS spectrum phenotypes. We used three motor scales and selected cognitive tests in a series of three males and three females from a single sibship carrying PM or GZ alleles (44 to 75 repeats). The molecular profiles from these siblings were determined by genomewide association study with single-nucleotide polymorphism (SNP) genotyping by Illumina Global Screening Array. Nonparametric linkage analysis was applied and Parkinson’s disease (PD) polygenic risk scores (PRSs) were calculated for all the siblings, based on 107 known risk variants. All male and female siblings manifested similar kinetic tremor phenotypes. In contrast to FXTAS, they showed negligible gait ataxia, and few white matter lesions on MRI. Cognitive functioning was unaffected. Suggestive evidence of linkage to a broad region of the short arm of chromosome 10 was obtained, and median PD PRS for the sibship fell within the top 30% of a sample of over 500,000 UK and Australian controls. The genomewide study results are suggestive of modifying effects of genetic risk loci linked to PD, on the neurological phenotype of FMR1-CGG small expansion carriers, resulting in an oligosymptomatic kinetic tremor seen in FXTAS spectrum, but also consistent with essential tremor.

Ataxia encompasses a large group of rare disorders characterized by irregular movements, decreased coordination, imbalance, kinetic tremor, wide-based stance, and dysarthria. Evaluating ataxia can be challenging considering the volume of disorders and their complex pathologies involving diverse genetic and clinical factors. This is a comprehensive review of the genetic ataxia literature, presenting updated guidelines for differential diagnosis. Age, time course, and family history provide initial guidance for evaluation of ataxia. As genetic testing is increasingly utilized, new genes are discovered and phenotypes for existing disorders are expanded. This review assists physicians by offering a diagnostic roadmap for suspected hereditary ataxia based on the current literature.

Background Facial (lip and jaw) tremor (FT) is associated with Parkinson’s disease (PD) but few studies have been conducted to explore its clinical profile. We performed this study to investigate the prevalence and clinical correlates of FT in PD, and further to evaluate its effect on disease progression. Methods A retrospective, cross-sectional (n = 2224) and longitudinal (n = 674) study was conducted. The presence of FT was based on a ≥ 1 score in the United PD Rating Scale (UPDRS) item 20A. Group comparisons were conducted, followed by a forward binary logistic regression analysis. Inverse probability of treatment weighting (IPTW) based on the propensity score and weighted or unweighted Cox regression models were used to explore the impact of FT on five clinical milestones including death, UPDRS III 11-point increase, Hoehn and Yahr (H&Y) stage reaching 3, dyskinesia development, and Montreal Cognitive Assessment 3-point decrease. Results FT was presented in 403 patients (18.1%), which showed increasing trends with disease duration and H&Y score. Age (P P P = 0.001), speech (P = 0.011), rigidity (P = 0.026), rest tremor on limbs (P P P = 0.013) were independent factors associated with FT. Both unweighted and weighted Cox regression models indicated that baseline FT and FT as the initial symptom were not associated with the five outcomes. Conclusions Our study suggested that FT was not uncommon and provided a deeper insight into the characteristics of FT in PD. The predict value of FT on long-term progronis of PD may need future longer follwe-up study.

Background: Despite the significance of tremor in Parkinson’s disease (PD) diagnosis, classification, and patient’s quality of life, there is a relative lack of data on prevalence and relationship of different tremor types in PD. Methods: The presence of rest tremor (RT) and action tremor (AT; defined as combination of both postural and kinetic tremor) was determined and RT severity was defined using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) at baseline in the Progression Marker Initiative (PPMI, n = 423), the Fox Investigation for New Discovery of Biomarkers (BioFIND, n = 118) and the Parkinson’s Disease Biomarkers Program (PDBP, n = 873) cohorts. Results: Across baseline data of all three cohorts, RT prevalence (58.2%) was higher than AT prevalence (39.0%). Patients with RT had significantly higher (Chi-square test, p < 0.05) prevalence of AT compared to patients without RT in the PPMI (40.0% versus 30.1%), BioFIND (48.0% versus 40.0%) and PDBP (49.9% versus 21.0%) cohorts. Furthermore, patients with AT had significantly (Student t-test, p < 0.05) higher RT severity that those without AT in PPMI (5.7 ± 5.4 versus 3.9 ± 3.3), BioFIND, 6.4 ± 6.3 versus 3.8 ± 4.4) and PDBP (6.4 ± 6.6 versus 3.7 ± 4.4) cohorts. In the BioFIND cohort, the prevalence of all types of tremor and their combinations significantly decreased from the off-state to on-state. Discussion: The RT is the most frequent tremor type and present in more than half of the PD patients. However, AT is also present in nearly one-third of the PD patients. Our results also indicate that RT and AT may have cross-interactions in PD, and that dopaminergic treatment influences both RT and AT.

BackgroundDespite the significance of tremor in Parkinson’s disease (PD) diagnosis, classification, and patient’s quality of life, there is a relative lack of data on prevalence and relationship of different tremor types in PD.MethodsThe presence of rest tremor (RT) and action tremor (AT; defined as combination of both postural and kinetic tremor) was determined and RT severity was defined using the Movement Disorders Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) at baseline in the Progression Marker Initiative (PPMI, n=423), the Fox Investigation for New Discovery of Biomarkers (BioFIND, n=118) and the Parkinson’s Disease Biomarkers Program (PDBP, n=873) cohorts.ResultsAcross baseline data of all three cohorts, RT prevalence (58.2%) was higher than AT prevalence (39.0%). Patients with RT had significantly higher (Chi-square test, pDiscussionThe RT is the most frequent tremor type and present in more than half of the PD patients. However, AT is also present in nearly one-third of the PD patients. Our results also indicate that RT and AT may have cross-interactions in PD.

Introduction In vivo dopamine transporter imaging is a useful tool for distinguishing nigrostriatal pathologies (e.g. Parkinson's disease) from other causes of tremor. However, while many of the motoric features of Parkinson's disease (e.g. bradykinesia, rigidity, hypomimia) correlate well with reduced striatal dopamine transporter binding, the same relationship has not been demonstrated for tremor. We investigated the relationship between striatal dopamine transporter binding and quantitative measures of tremor. Methods 23 participants with Parkinson's disease underwent standardised clinical assessment including structured, videotaped clinical examination, tremor neurophysiology study of both upper limbs using accelerometry and surface EMG, and Technitium-99 m TRODAT-1 brain SPECT imaging. Normalised striatal uptake values were calculated. Tremor EMG and accelerometry time series were processed with Fourier transformation to identify peak tremor power within a window of 3–10Hz and to calculate the tremor stability index (TSI). Results Spearman correlation analyses revealed an association between tremor power and contralaterally reduced striatal uptake in a number of recording conditions. This association was strongest for rest tremor, followed by postural tremor, with the weakest association observed for kinetic tremor. Lower TSI was also associated with lower contralateral striatal uptake in a number of rest and postural conditions. Conclusion These data suggest a relationship between Parkinsonian rest tremor and contralateral reduction in striatal dopamine binding. Use of quantitative neurophysiology techniques may allow the demonstration of clinico-pathophysiological relationships in tremor that have remained occult to previous studies.

Background Essential tremor (ET) is now considered as a slowly progressive neurodegenerative disorder with a variety of motor and non-motor manifestations. The objectives of this work were to study the existence of cognitive, mood, olfactory, and balance dysfunctions in ET patients and their relation to tremor severity as well as patients’ activity of daily livings. Methods This study was performed on 36 ET patients and 24 healthy controls subjects (HCS) submitted to The Essential Tremor Rating Assessment Scale (TETRAS), advanced activity of daily living scale (AADLs), Montreal cognitive assessment scale (MoCA), Montgomery–Åsberg Depression Rating Scale (MADRS), auditory mismatch negativity (MMN), Sniffin’ Sticks test (SST), computerized dynamic posturography (CDP), and brain MRI diffusion tensor tractography (DTT). Results ET patients showed significant decrease in AADLs, MoCA, SST (threshold, identification, and discrimination subscales) as well as visual and vestibular ratios of CDP compared to HCS. Auditory MMN showed significant reduction in the amplitude and prolongation of latencies while corticospinal tracts, thalamo-cortical connectivity, and middle cerebellar peduncles DTT revealed reduced fractional anisotropy in ET patients with normal tracts densities. Conclusion ET patients exhibit a wide variety of non-motor manifestations including cognitive impairment, depressive symptoms, hyposmia, and increased risk of falls with consecutive reduced activity of daily living beyond the deleterious effects of the kinetic tremor.

Essential tremor (ET) is one of the most common movement disorders and the prototypical disorder for abnormal rhythmic movements. However, the pathophysiology of tremor generation in ET remains unclear. Here, we used autoptic cerebral tissue from patients with ET, clinical data, and mouse models to report that synaptic pruning deficits of climbing fiber (CF)-to-Purkinje cell (PC) synapses, which are related to glutamate receptor delta 2 (GluRδ2) protein insufficiency, cause excessive cerebellar oscillations and might be responsible for tremor. The CF-PC synaptic pruning deficits were correlated with the reduction in GluRδ2 expression in the postmortem ET cerebellum. Mice with GluRδ2 insufficiency and CF-PC synaptic pruning deficits develop ET-like tremor that can be suppressed with viral rescue of GluRδ2 protein. Step-by-step optogenetic or pharmacological inhibition of neuronal firing, axonal activity, or synaptic vesicle release confirmed that the activity of the excessive CF-to-PC synapses is required for tremor generation. In vivo electrophysiology in mice showed that excessive cerebellar oscillatory activity is CF dependent and necessary for tremor and optogenetic-driven PC synchronization was sufficient to generate tremor in wild-type animals. Human validation by cerebellar electroencephalography confirmed that excessive cerebellar oscillations also exist in patients with ET. Our findings identify a pathophysiologic contribution to tremor at molecular (GluRδ2), structural (CF-to-PC synapses), physiological (cerebellar oscillations), and behavioral levels (kinetic tremor) that might have clinical applications for treating ET.

Objective. This study was aimed at identifying the potential outcome predictors, comparing the efficacy in patients with different tremor characteristics, and summarizing the adverse effect rates (AERs) of deep brain stimulation on the ventral intermediate nucleus (VIM-DBS) for essential tremor (ET). Methods. An extensive search of articles published to date in 2019 was conducted, and two main aspects were analyzed. Improvement was calculated as a percentage of change in any objective tremor rating scale (TRS) and analyzed by subgroup analyses of patients’ tremor characteristics, laterality, and stimulation parameters. Furthermore, the AERs were analyzed as follows: the adverse effects (AEs) were classified as stimulation-related, surgical-related, or device-related effects. A simple regression analysis was used to identify the potential prognostic factors, and a two-sample mean-comparison test was used to verify the statistical significance of the subgroup analyses. Results. Forty-six articles involving 1714 patients were included in the meta-analysis. The pooled improvement in any objective TRS score was 61.3% (95% CI: 0.564-0.660) at the mean follow-up visit (20.0±17.3 months). The midline and extremity symptoms showed consistent improvement (P=0.440), and the results of the comparison of postural and kinetic tremor were the same (P=0.219). In addition, the improvement in rest tremor was similar to that in action tremor (OR=2.759, P=0.120). In the simple regression analysis, the preoperative Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) scores and follow-up time were negatively correlated with the percentage change in any objective TRS score (P<0.05). The most common adverse event was dysarthria (10.5%), which is a stimulation-related AE (23.6%), while the rates of the surgical-related and device-related AEs were 6.4% and 11.5%, respectively. Conclusion. VIM-DBS is an efficient and safe surgical method in ET, and the efficacy was not affected by the body distribution of tremor, age at surgery, and disease duration. Lower preoperative FTM-TRS scores likely indicate greater improvement, and the effect of VIM-DBS declines over time.

Introduction Essential tremor-Parkinson's disease (ET-PD) syndrome is a clinical condition in which individuals with a long-lasting history of Essential tremor (ET) eventually develop Parkinson's disease (PD). The aim of the study was to investigate the accuracy performances of clinical, neurophysiological, and imaging biomarkers in differentiating patients affected by ET-PD syndrome from patients with ET or PD. Methods Nineteen patients affected by ET-PD syndrome, 48 ET patients, and 37 tremor-dominant PD (t-PD) patients were included. Electrophysiological studies, including blink-reflex recovery cycle and tremor parameters analyses, were performed in all groups. Nigro-striatal and cardiac sympathetic denervation were also investigated. Sensitivity, specificity and accuracy of clinical, electrophysiological, and radiological features in differentiating ET-PD syndrome from ET and PD were calculated. Results ET-PD patients had significantly lower rigidity (p = 0.007) and higher postural/kinetic tremor (p = 0.007) scores, in comparison to t-PD patients. ET-PD patients, differently from PD patients, had a synchronous pattern of resting tremor and, differently from ET patients, had abnormal blink-reflex recovery cycle. ET-PD patients also showed reduced nigro-striatal and cardiac sympathetic uptakes, albeit to a lesser extent than in PD patients. The highest accuracy values were found for the synchronous pattern of resting tremor (97.1%) in distinguishing ET-PD from PD, and for presence of abnormal blink-recovery cycle (100%) in distinguishing ET-PD syndrome from ET. Conclusion Our study demonstrates that some electrophysiological parameters, such as a synchronous resting tremor pattern and the abnormal blink-recovery cycle were the most accurate biomarkers in distinguishing patient with ET-PD syndrome from those with ET or those with PD.

Background Clinical and anecdotal observations propose that patients with Parkinson's disease (PD) may show drug-induced dyskinesia (DID) concomitantly with cardinal motor features. However, the extent of the concomitant presence of DID and cardinal features remains to be determined. Objectives This cross-sectional study measured peak-dose choreic-type DID in a quantitative manner in patients diagnosed with PD, and determined whether symptoms such as tremor, bradykinesia, rigidity, postural instability or freezing of gait (FoG) were still detectable in these patients. Methods 89 patients diagnosed with PD were recruited and assessed using a combination of quantitative measures using inertial measurement units to capture DID, tremor, bradykinesia, and FoG. Clinical evaluations were also used to assess rigidity and postural instability. Motor symptoms of PD were assessed 3 times during the testing period, and a series of activities of daily living were repeated twice, in between clinical tests, during which the level of DID was quantified. Peak-dose was identified as the period during which patients had the highest levels of DID. Levels of tremor, rigidity, bradykinesia, postural instability, and FoG were used to determine the percentage of patients showing these motor symptoms simultaneously with DID. Results 72.4% of patients tested presented with measurable DID during the experiment. Rest, postural and kinetic tremor (12.7% , 38.1% , and 15.9% respectively), bradykinesia (28.6% ), rigidity (55.6% ), postural instability (71.4% ) and FoG (9.5% ) were detected simultaneously with DID. Conclusions PD symptomatology remains present in patients showing peak-dose choreic-type DID, illustrating the challenge facing physicians when trying to avoid dyskinesia while attempting to alleviate motor symptoms.

Introduction. Essential tremor (ET) is one of the most common movement disorders. It is mainly characterized by postural and kinetic tremor, affecting arms and other body parts. Progression of ET violates social activity, lowers self-esteem, and occasionally leads to the patient’s disability. Selection of an effective drug therapy for ET is mostly carried out empirically and takes long time, which causes additional negative psycho-emotional effects, distrust of the doctor and abandonment of the treatment. Present study is aimed at the implementing a novel approach to the segregation of ET subtypes based on the heterogeneity of the pharmacological response. Results. Neuroanatomical, electrophysiological and biochemical data published to date are outlined in the current paper, to designate parameters for identification of ET subtypes with deterministic pharmacological response. Before prescribing pharmacotherapy for patients with ET, it is necessary to perform asurface electromyography to identify the patterntype of antagonist muscles contractions. In addition, the concentration of glutamate and gamma-aminobutyric acid in peripheral blood should be determined. Conclusion. The heterogeneity of pharmacological response among patients with ET necessitates a more subtle classification within the syndrome by neuroanatomical, electrophysiological and biochemical indicators. The approach proposed in the review will increase the effectiveness of therapy and improve the lifequality of patients with ET. (For citation: Muruzheva ZM, Karpenko MN, Klimenko VM. The heterogeneity of drug response as the basis of identificationof essential tremor subtypes. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):54-59. doi: 10.17816/RCF16154-59).