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.

Lack of Familial Aggregation of the "Essential Tremor-Plus" Phenotype in Familial Essential Tremor.

BACKGROUND: Essential tremor (ET) is a highly prevalent neurological disease that frequently runs in families. A recent and controversial proposal is to separate ET patients into two distinct groups - ET versus ET-plus. If this were a valid construct, one would expect in familial aggregation studies to observe that ET-plus would cluster in some families yet be absent in others, rather than being randomly distributed across families. We examined whether there is evidence of familial aggregation of ET-plus. METHODS: Probands (n = 84 [56 ET-plus and 28 ET]) and their first- and second-degree relatives (n = 182 and 48) enrolled in a genetics study. χ2 and generalized estimating equations (GEE) tested associations between probands' ET-plus status and the ET-plus status of their relatives. RESULTS: χ2 analyses revealed that ET-plus was no more prevalent in relatives of probands diagnosed with ET-plus than in relatives of probands diagnosed with ET, p > 0.05. Restricting relatives to first-degree relatives similarly did not detect a significant association (p = 0.88). GEE yielded similar results (respective p's = 0.39 and 0.81). CONCLUSION: The data demonstrate that ET-plus does not seem to aggregate in families. As such, they do not lend support to the notion that ET-plus is a valid biological construct.

Evaluation of rest tremor in different positions in Parkinson's disease and essential tremor plus.

BACKGROUND: Rest tremor (RT) can be observed in several positions (seated, standing, lying down) but it is unknown whether the tremor features may vary across them. This study aimed to compare the RT electrophysiological features across different positions in tremor-dominant Parkinson's disease (PD) and essential tremor plus (ET with RT, rET). METHODS: We consecutively enrolled 90 tremor-dominant PD and 24 rET patients. The RT presence was evaluated in three positions: with the patient seated, the arm flexed at 90°, the forearm supported against gravity, and the hand hanging down from the chair armrest (hand-hanging position), in lying down supine and in standing position. RT electrophysiological features (amplitude, frequency, burst duration, pattern) were compared between the two patient groups and across the different positions. RESULTS: All PD and rET patients showed RT in hand-hanging position. Supine and standing RT were significantly more common in PD (67.8% and 75.6%, respectively) than in rET patients (37.5% and 45.8%, respectively). RT amplitude, frequency and pattern were significantly different between groups in hand-hanging position whereas only pattern was significantly different between PD and rET in both standing and supine positions. In each patient group, all RT electrophysiological features did not significantly vary across different recording positions (p > 0.05). DISCUSSION: In our study, PD and rET showed RT in hand-hanging, supine, and standing positions. RT pattern was the only electrophysiological feature significantly different between PD and rET patients in all these positions, enabling clinicians to perform the RT analysis for diagnostic purposes in different tremor positions.

"Essential Tremor Plus": A Problematic Concept: Implications for Clinical and Epidemiological Studies of Essential Tremor.

BACKGROUND: An issue of central importance for most neurological disorders is that of case definition. In the field of neuroepidemiology, case definition informs the design, conduct, and interpretation of research studies that range from observational to interventional studies, from case-control to cohort studies, and from descriptive to analytical studies. For essential tremor (ET), one of the most common neurological disorders, the issue of case definition is particularly important. Though traditionally viewed as a monochromatic disorder, recent years have seen an expansion of the clinical phenotype. In a recently proposed consensus statement on tremor, a proposal was made to separate from ET a new tentatively and uncertainly-defined entity characterized by the presence of additional neurological signs other than action tremor. This entity would be termed "ET-plus". The aims of this invited paper are to discuss the impact of the proposed nomenclature on studies of ET neuroepidemiology. SUMMARY: The proposed term "ET-plus" is based solely on clinical features and even these are not clearly defined. It is not based on differences in underlying etiology (e.g., genes) or pathology. As such, it is not grounded in underlying biological differences. The use of the term would have numerous research implications. As detailed here, it would greatly complicate or make impossible studies of the descriptive epidemiology of ET, association studies, cohort studies, and clinical trials in ET. Key Messages: The proposed designation has the potential to be very problematic for studies of the epidemiology of tremor. This, along with this questionable validity of the proposed nomenclature, calls its use into serious question.

Clinical characteristics of patients with essential tremor or essential tremor plus.

BACKGROUND: The International Parkinson and Movement Disorder Society introduced the category of essential tremor (ET)-plus in its new ET classification scheme, but how the clinical correlates of ET-plus differ from those of "pure" ET is unclear. By comparing the clinical characteristics of ET and ET-plus patients, we expect to better understand the impact and invoked questions of the new classification on clinical practice. METHODS: We reviewed the medical records of 280 ET syndrome patients in an ongoing cross-sectional study in a Chinese population and reclassified them according to the new criteria. Clinico-demographic characteristics were compared between ET and ET-plus patients. Risk factors of diagnosis of ET-plus were explored using logistic regression. RESULTS: A total of 121 patients (50.8%) were reclassified as having ET and 117 as having ET-plus. ET-plus group was significantly older at tremor onset, less educated, and more likely to have cranial tremor, depression symptom, anxiety symptom, and probable REM sleep behavior disorder. ET-plus group also showed more severe upper limb tremor and cognition impairment. Regression analysis identified four independent risk factors associated with ET-plus: late tremor onset (OR 3.04, 95%CI 1.60-5.79), less educated (OR 0.91, 95%CI 0.85-0.97), severe upper limb tremor (OR 2.46, 95%CI 1.30-4.62), and presence of cranial tremor (OR 2.30, 95%CI 1.20-4.41). CONCLUSIONS: The new classification scheme emphasized that ET syndrome is heterogeneous. ET-plus cannot be seen as a subtype or a diagnosis of ET syndrome, but rather as a placeholder, representing an area of current scientific uncertainty.

Features in essential tremor and the development of Parkinson's disease vs. parkinsonism.

BACKGROUND: Patients with essential tremor (ET) are at higher risk to develop Parkinson's disease (PD). Recent studies suggest that propranolol (common treatment for ET) can augment pathologic expression of alpha-synuclein. We studied features associated with the development of Parkinson's disease with antecedant essential tremor (ET-PD) compared with ET-plus with parkinsonism (PK). DESIGN: Retrospective case series from a tertiary movement disorders center including patients with ET and PD, found to have ET-PD or ET-plus (PK). RESULTS: We analyzed two groups: (1) ET-plus (PK) (n = 33) and (2) ET-PD (n = 35). Constipation and anosmia were more common in the ET-PD group (73% and 48%) than in the ET-plus (PK) group (33% and 19%). The ET-plus (PK) group was more likely to undergo dopamine transporter (DAT) scans compared with the ET-PD group (73% vs. 34%) and less likely to receive levodopa trials (21% vs. 91%). There were no significant differences in self-reported REM sleep behavior disorders or beta-blocker use. Similar rates of depression, anxiety, cognitive complaints, and family history of tremor or PD were reported in both groups. CONCLUSION: ET-PD and ET-plus (PK) can be clinically difficult to differentiate as they have overlapping motor and non-motor features. Beta-blocker use did not predict development of ET-PD or ET-plus (PK); however, anosmia and constipation may be helpful non-motor distinguishing features. DAT scans and levodopa trials may be valuable in clarifying the diagnoses.

Essential Tremor and Essential Tremor Plus Are Essentially Similar Electrophysiologically.

BACKGROUND: The merits of classifying the heterogeneous group of essential tremors into essential tremor (ET) and essential tremor plus (ETP) are debated. OBJECTIVES: We studied the electrophysiological and spiral characteristics of tremor in ET and ETP. METHODS: We reviewed standardized videos from a tremor database and clinically classified patients into ET, ETP, or dystonic tremor (DT). The following variables were derived from combined tri-axial accelerometry-surface electromyography (EMG)-peak frequency, total power, peak power, full width half maximum, tremor stability index and EMG-coherence. We analyzed hand-drawn spirals to derive mean deviation, tremor variability, inter-, and intra-loop widths. We compared these variables among the groups. RESULTS: We recruited 72 participants (81.9% male) with mean age 47.7 ± 16.1 years and Fahn-Tolosa-Marin Tremor Rating Scale total score 31.1 ± 14.1. Patients with ET were younger (P = 0.014) and had less severe tremor (P = 0.020) compared to ETP and DT. In ETP group, 48.6% had subtle dystonia. Peak frequency was greater in ETP (7.3 ± 0.3 Hz) compared to DT (6.1 ± 0.4 Hz; P = 0.024). Peak power was greater in ETP and DT for postural tremor. Rest tremor was recordable on accelerometry in 26.7% of ET. Other variables were similar among the groups. CONCLUSION: Electrophysiological evaluation revealed postural tremor of frequency 6 to 7 Hz in ET, ETP, and DT with subtle differences more severe tremor in ETP and DT, and higher frequency in ETP compared to DT. Our findings suggest a similar tremor oscillator in these conditions, supporting the view that these entities are part of a spectrum of tremor disorders, rather than distinct etiological entities.

Comparing Essential Tremor with and without Soft Dystonic Signs and Tremor Combined with Dystonia: The TITAN Study.

BACKGROUND: Tremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non-parkinsonian tremors is relatively high. OBJECTIVES: To compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD). METHODS: We compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life. RESULTS: Three-hundred-eighty-three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task-specificity, and position-dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable "group", independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor. CONCLUSIONS: Pure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra-group heterogeneity.

Multimodal imaging and electrophysiological study in the differential diagnosis of rest tremor.

Introduction: Distinguishing tremor-dominant Parkinson's disease (tPD) from essential tremor with rest tremor (rET) can be challenging and often requires dopamine imaging. This study aimed to differentiate between these two diseases through a machine learning (ML) approach based on rest tremor (RT) electrophysiological features and structural MRI data. Methods: We enrolled 72 patients including 40 tPD patients and 32 rET patients, and 45 control subjects (HC). RT electrophysiological features (frequency, amplitude, and phase) were calculated using surface electromyography (sEMG). Several MRI morphometric variables (cortical thickness, surface area, cortical/subcortical volumes, roughness, and mean curvature) were extracted using Freesurfer. ML models based on a tree-based classification algorithm termed XGBoost using MRI and/or electrophysiological data were tested in distinguishing tPD from rET patients. Results: Both structural MRI and sEMG data showed acceptable performance in distinguishing the two patient groups. Models based on electrophysiological data performed slightly better than those based on MRI data only (mean AUC: 0.92 and 0.87, respectively; p = 0.0071). The top-performing model used a combination of sEMG features (amplitude and phase) and MRI data (cortical volumes, surface area, and mean curvature), reaching AUC: 0.97 ± 0.03 and outperforming models using separately either MRI (p = 0.0001) or EMG data (p = 0.0231). In the best model, the most important feature was the RT phase. Conclusion: Machine learning models combining electrophysiological and MRI data showed great potential in distinguishing between tPD and rET patients and may serve as biomarkers to support clinicians in the differential diagnosis of rest tremor syndromes in the absence of expensive and invasive diagnostic procedures such as dopamine imaging.

Combined cortical thickness and blink reflex recovery cycle to differentiate essential tremor with and without resting tremor.

Objective: To investigate the performance of structural MRI cortical and subcortical morphometric data combined with blink-reflex recovery cycle (BRrc) values using machine learning (ML) models in distinguishing between essential tremor (ET) with resting tremor (rET) and classic ET. Methods: We enrolled 47 ET, 43 rET patients and 45 healthy controls (HC). All participants underwent brain 3 T-MRI and BRrc examination at different interstimulus intervals (ISIs, 100-300 msec). MRI data (cortical thickness, volumes, surface area, roughness, mean curvature and subcortical volumes) were extracted using Freesurfer on T1-weighted images. We employed two decision tree-based ML classification algorithms (eXtreme Gradient Boosting [XGBoost] and Random Forest) combining MRI data and BRrc values to differentiate between rET and ET patients. Results: ML models based exclusively on MRI features reached acceptable performance (AUC: 0.85-0.86) in differentiating rET from ET patients and from HC. Similar performances were obtained by ML models based on BRrc data (AUC: 0.81-0.82 in rET vs. ET and AUC: 0.88-0.89 in rET vs. HC). ML models combining imaging data (cortical thickness, surface, roughness, and mean curvature) together with BRrc values showed the highest classification performance in distinguishing between rET and ET patients, reaching AUC of 0.94 ± 0.05. The improvement in classification performances when BRrc data were added to imaging features was confirmed by both ML algorithms. Conclusion: This study highlights the usefulness of adding a simple electrophysiological assessment such as BRrc to MRI cortical morphometric features for accurately distinguishing rET from ET patients, paving the way for a better classification of these ET syndromes.

The Spectrum of Non-Parkinsonian Tremor: A Registry at a Tertiary Care Teaching Institute.

Background: Tremors other than those associated with Parkinson's disease (non-parkinsonian tremor) are commonly observed in clinical settings. However, their frequency and clinical characteristics have rarely been reported. Objectives: To classify non-parkinsonian tremors based on the consensus statement on the classification of tremors, from the task force of the International Parkinson and Movement Disorder Society published in 2018. Methods: A prospective registry at a tertiary care teaching institute. Results: A total of 475 patients with non-parkinsonian tremors were recruited for the study. 67.57% (n = 321) of our patients were male and a family history of tremor was present in 20.84% (n = 99) of patients. Dystonic tremor (DT) was the most common non-parkinsonian tremor (33.26%). 27.78% of patients fulfilled the new classification criteria for essential tremor, with 13.47% classified as pure ET (ET) and 14.31% exhibiting neurological soft signs, leading to the classification of ET plus (ETP). Patients with ETP had more family history (57.35%) [vs DT (26.48%, p = 0.00004) and ET (10.93%, p = 0.00003], longer duration of disease [mean ± standard deviation (SD) = 9.53 ± 8.64 years] [vs DT (5.60 ± 5.93, p = 0.0003) and ET (6.38 ± 5.97, p = 0.01) years], and more severe tremor as measured by the essential tremor rating assessment scale total score [mean ± SD = 27.42 ± 11.70] [vs DT (23.50 ± 8.62, p = 0.007) and ET (22.12 ± 8.19, p = 0.007)] compared with patients with DT and ET. Conclusions: DT was the most common cause of non-parkinsonian tremor in our registry followed by essential tremor syndrome. ETP was more common than ET.

Deep brain stimulation for essential tremor versus essential tremor plus: should we target the same spot in the thalamus?

Background: Although ET is a phenomenologically heterogeneous condition, thalamic DBS appears to be equally effective across subtypes. We hypothesized stimulation sites optimized for individuals with essential tremor (ET) would differ from individuals with essential tremor plus syndrome (ET-plus). We examined group differences in optimal stimulation sites within the ventral thalamus and their overlap of with relevant white matter tracts. By capturing these differences, we sought to determine whether ET subtypes are associated with anatomically distinct neural pathways. Methods: A retrospective chart review was conducted on ET patients undergoing VIM DBS at MUSC between 01/2012 and 02/2022. Clinical, demographic, neuroimaging, and DBS stimulation parameter data were collected. Clinical characteristics and pre-DBS videos were reviewed to classify ET and ET-plus cohorts. Patients in ET-plus cohorts were further divided into ET with dystonia, ET with ataxia, and ET with others. DBS leads were reconstructed using Lead-DBS and the volume of tissue activated (VTA) overlap was performed using normative connectomes. Tremor improvement was measured by reduction in a subscore of tremor rating scale (TRS) post-DBS lateralized to the more affected limb. Results: Sixty-eight ET patients were enrolled after initial screening, of these 10 ET and 24 ET-plus patients were included in the final analyses. ET group had an earlier age at onset (p = 0.185) and underwent surgery at a younger age (p = 0.096). Both groups achieved effective tremor control. No significant differences were found in lead placement or VTA overlap within ventral thalamus. The VTA center of gravity (COG) in the ET-plus cohort was located dorsal to that of the ET cohort. No significant differences were found in VTA overlap with the dentato-rubral-thalamic (DRTT) tracts or the ansa lenticularis. Dystonia was more prevalent than ataxia in the ET-plus subgroups (n = 18 and n = 5, respectively). ET-plus with dystonia subgroup had a more medial COG compared to ET-plus with ataxia. Conclusion: VIM DBS therapy is efficacious in patients with ET and ET-plus. There were no significant differences in optimal stimulation site or VTA overlap with white-matter tracts between ET, ET-plus and ET-plus subgroups.

Grey matter correlates of dystonic soft signs in essential tremor.

BACKGROUND: Questionable signs of dystonia are a common finding in patients with essential tremor (ET). Brain structural alterations in ET patients plus dystonic soft signs (ET + ds) in comparison to ET patients without dystonic soft signs (ET-ds) or patients with tremor associated with manifest dystonia (TAWD) have not been examined yet. Therefore, our study aims to explore alterations of brain grey matter in patients with ET + ds. METHODS: A total of 68 elderly patients with ET-ds (n = 32), ET + ds (n = 20) or idiopathic cervical dystonia with dystonia associated action tremor of the upper limbs (TAWD, n = 16) and 42 age-matched healthy controls underwent a clinical and electrophysiological assessment and 3T MRI. For grey matter alterations T1 MRI images were analysed by voxel-based morphometry. Additionally, regression analyses with clinical parameters (tremor frequency, severity and disease duration) were performed. RESULTS: VBM showed a significant increase of grey matter in the right lentiform nucleus in ET + ds and TAWD compared to HC and ET-ds. Further, an increase of cortical grey matter in the middle frontal gyrus in ET + ds was shown. The hypertrophy of the lentiform nucleus in ET + ds was correlated with disease severity and duration. CONCLUSION: Patients with ET + ds showed grey matter brain structural alterations similar to TAWD. Our findings suggest an involvement of the basal ganglia-cortical loop in ET + ds which may indicate a pathophysiological similarity with TAWD rather than ET.

Cortical involvement in essential tremor with and without rest tremor: a machine learning study.

INTRODUCTION: There is some debate on the relationship between essential tremor with rest tremor (rET) and the classic ET syndrome, and only few MRI studies compared ET and rET patients. This study aimed to explore structural cortical differences between ET and rET, to improve the knowledge of these tremor syndromes. METHODS: Thirty-three ET patients, 30 rET patients and 45 control subjects (HC) were enrolled. Several MR morphometric variables (thickness, surface area, volume, roughness, mean curvature) of brain cortical regions were extracted using Freesurfer on T1-weighted images and compared among groups. The performance of a machine learning approach (XGBoost) using the extracted morphometric features was tested in discriminating between ET and rET patients. RESULTS: rET patients showed increased roughness and mean curvature in some fronto-temporal areas compared with HC and ET, and these metrics significantly correlated with cognitive scores. Cortical volume in the left pars opercularis was also lower in rET than in ET patients. No differences were found between ET and HC. XGBoost discriminated between rET and ET with mean AUC of 0.86 ± 0.11 in cross-validation analysis, using a model based on cortical volume. Cortical volume in the left pars opercularis was the most informative feature for classification between the two ET groups. CONCLUSION: Our study demonstrated higher cortical involvement in fronto-temporal areas in rET than in ET patients, which may be linked to the cognitive status. A machine learning approach based on MR volumetric data demonstrated that these two ET subtypes can be distinguished using structural cortical features.

Is essential tremor a family of diseases or a syndrome? A syndrome.

In a consensus statement, a task force of the "International Parkinson and Movement Disorder Society" (IPMDS) has recently proposed a two axes classification for tremor: axis I (clinical manifestations) and axis II (etiology). In the axis, I, the clinical features of tremor in a given patient are specified in terms of medical history, tremor characteristics, associated signs, and laboratory tests for some tremors leading to the discovery of axis 2 etiologies. Based on axis I sign and symptoms a specific clinical syndrome is diagnosed which have been categorized as isolated tremor syndrome (a syndrome consisting only of tremor) and combined tremor syndrome (consisting of tremor and other systemic or neurological signs). The IPMDS task force defined essential tremor as an isolated tremor syndrome of bilateral upper limb action tremor of at least 3years duration with or without a tremor in other locations (e.g., head, voice or lower limbs) in absence of other neurological signs, such as dystonia, ataxia, or parkinsonism. Patients with neurological signs of uncertain significance (such as impaired tandem gait, questionable dystonic posturing, or memory impairment) are classified as essential tremor plus. In this paper, the author will make the argument that essential tremor is a syndrome with multiple causes.

Reclassification of patients with tremor syndrome and comparisons of essential tremor and essential tremor-plus patients.

BACKGROUND: The new essential tremor (ET)-plus nomenclature was proposed by the 2018 Tremor Consensus Criteria. However, few studies have adopted this usage and the clinical differences between ET and ET-plus remains unclear. To address this issue, we reclassified and compared the characteristics of ET and ET-plus patients in a large Chinese tremor cohort. METHODS: In this cross-sectional observational study, 766 patients originally diagnosed with ET underwent neurological examination. Scale ratings were used to evaluate motor and non-motor symptoms, and quality of life (QoL). We then reclassified the ET cohort and compared demographic and clinical characteristics between ET and ET-plus patients. A logistic regression analysis was used to explore whether the presence of neurological soft signs in ET-plus was associated with tremor severity or QoL. RESULTS: Among 665 clinically confirmed ET syndrome patients, 274 were ET and 391 were ET-plus. The most prevalent neurological soft sign was resting tremor. ET-plus patients were older, had older age at onset and longer disease duration. ET-plus patients recorded higher scores in tremor severity evaluations and lower in cognitive evaluations, whereas a higher proportion of patients presented with depression or anxiety symptoms. Resting tremor and questionable cerebellar signs were associated with tremor severity. Cognitive impairment was associated with worse QoL. CONCLUSIONS: ET-plus patients were older, had longer disease durations, worse tremor manifestations, and more distinct non-motor symptoms. Certain additional soft signs of ET-plus were associated with tremor severity or worse QoL. ET-plus patients may include advanced ET patients with additional neurological soft signs presenting along with disease progression.

The MDS consensus tremor classification: The best way to classify patients with tremor at present.

In 2018, the new Consensus Statement on the Classification of Tremors, by the Task Force on Tremor of the International Parkinson Movement Disorder Society, was published. So far, the article has been cited more than 400 times in peer-reviewed international journals and commonly debated in conferences and meetings due to an enthusiastic welcome from the community. Compared to the previous Consensus Statement (1998), the main novelties are: 1) the classification of tremor according to clinical manifestation (Axis 1) and etiology (Axis 2), and therefore the use of a syndromic approach; 2) the definition of essential tremor as a syndrome; 3) the recognition of the new category essential tremor plus, that derives from the uncertain significance of the soft neurological signs often associated with essential tremor. In this paper, we summarise and explain the most important aspects of the new classification of tremors, highlighting the main novelties, their relevance, and application in clinical practice. Moreover, we discuss its possible weakness and reflect on the critical comments made so far. We believe that this new tremor classification is comprehensive, rigorous, and consistent and, considering our current knowledge of tremor syndromes, it is the best we can do at present. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.

Problems and controversies in tremor classification.

The Consensus Statement on the Classification of Tremors, from the Task Force of the International Parkinson's and Movement Disorder Society was published in 2018 in response to advances in the understanding of essential tremor (ET), tremor associated with dystonia and other monosymptomatic and indeterminate tremors. This was a revision of the previous 1998 Consensus Statement. A number of problems arise from this classification and, in this manuscript, we highlight several of these. These problems relate to the definition of tremor, the definition of ET, the proposal of the term 'essential tremor plus', issues related to orthostatic tremor (OT) including the proposal of the term 'orthostatic tremor plus', and the absence of a hierarchy of terms used to classify tremor. Among the proposals we make is that the definition of tremor should acknowledge that tremor is a symptom, ET should be redefined, severity is an important characteristic for classifying and diagnosing tremor, the terms 'essential tremor plus' and 'orthostatic tremor plus' should be abandoned, and classification of tremor requires rules for creating a hierarchy of terminology. "This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh".

Tremor Syndromes: An Updated Review.

Tremor is the most commonly encountered movement disorder in clinical practice. A wide range of pathologies may manifest with tremor either as a presenting or predominant symptom. Considering the marked etiological and phenomenological heterogeneity, it would be desirable to develop a classification of tremors that reflects their underlying pathophysiology. The tremor task force of the International Parkinson Disease and Movement Disorders Society has worked toward this goal and proposed a new classification system. This system has remained a prime topic of scientific communications on tremor in recent times. The new classification is based on two axes: 1. based on the clinical features, history, and tremor characteristics and 2. based on the etiology of tremor. In this article, we discuss the key aspects of the new classification, review various tremor syndromes, highlight some of the controversies in the field of tremor, and share the potential future perspectives.