Challenges in Describing Tremor and Dystonia.

Tremor is defined as an oscillatory and rhythmical movement. By contrast, dystonia is defined by sustained or intermittent abnormal postures, repetitive movements, or both. Tremor and dystonia often coexist in the same individual.

Associations Among Tremor Amplitude, Activities of Daily Living, and Quality of Life in Patients with Essential Tremor.

Background: Essential tremor (ET) is a disabling syndrome consisting of tremor, primarily in the upper limbs. We assessed the correlation of The Essential Tremor Rating Assessment Scale (TETRAS) Performance Item 4 ratings of upper limb tremor with the TETRAS activities of daily living (ADL) subscale and with 2 quality of life (QoL) scales.

Methods: This noninterventional, cross-sectional, point-in-time survey of neurologists(n = 60), primary care physicians (n = 38), and their patients with ET (n = 1,003) used real-world data collected through the Adelphi ET Disease Specific Programme™.

A Randomized Phase 2 KINETIC Trial Evaluating SAGE-324/BIIB124 in Individuals with Essential Tremor.

Background: SAGE-324/BIIB124 is an investigational positive allosteric modulator of GABA receptors.

Objective: KINETIC (NCT04305275), a double-blind, randomized, placebo-controlled, phase 2 study, evaluated SAGE-324/BIIB124 in individuals with essential tremor (ET).

Methods: Individuals aged 18 to 80 years were randomly assigned 1:1 to orally receive 60 mg of SAGE-324/BIIB124 or placebo once daily for 28 days.

Bayesian Interpretation of Essential Tremor Plus.

Essential tremor (ET) plus is a new tremor classification that was introduced in 2018 by a task force of the International Parkinson and Movement Disorder Society. Patients with ET plus meet the criteria for ET but have one or more additional systemic or neurologic signs of uncertain significance or relevance to tremor ("soft signs"). Soft signs are not sufficient to diagnose another tremor syndrome or movement disorder, and soft signs in ET plus are known to have poor interrater reliability and low diagnostic sensitivity and specificity.

Tremor rating scales and laboratory tools for assessing tremor.

The purpose of this review is to characterize and compare validated clinical rating scales and transducers that are used in the clinical assessment of tremor disorders. Tremor is an involuntary oscillatory movement of a body part. Tremor can be characterized in terms of amplitude and frequency of oscillation, and these kinematic properties vary randomly and with activities of daily living.

The clinical and electrophysiological investigation of tremor.

The various forms of tremor are now classified in two axes: clinical characteristics (axis 1) and etiology (axis 2). Electrophysiology is an extension of the clinical exam. Electrophysiologic tests are diagnostic of physiologic tremor, primary orthostatic tremor, and functional tremor, but they are valuable in the clinical characterization of all forms of tremor.

Head tremor in cervical dystonia: Quantifying severity with computer vision.

Background: Head tremor (HT) is a common feature of cervical dystonia (CD), usually quantified by subjective observation. Technological developments offer alternatives for measuring HT severity that are objective and amenable to automation.

Objectives: Our objectives were to develop CMOR (Computational Motor Objective Rater; a computer vision-based software system) to quantify oscillatory and directional aspects of HT from video recordings during a clinical examination and to test its convergent validity with clinical rating scales.

From null to midline: changes in head posture do not predictably change head tremor in cervical dystonia.

Introduction: A common view is that head tremor (HT) in cervical dystonia (CD) decreases when the head assumes an unopposed dystonic posture and increases when the head is held at midline. However, this has not been examined with objective measures in a large, multicenter cohort.

Methods: For 80 participants with CD and HT, we analyzed videos from examination segments in which participants were instructed to 1) let their head drift to its most comfortable position (null point) and then 2) hold their head straight at midline.

Evaluation of movement and brain activity.

Clinical neurophysiology studies can contribute important information about the physiology of human movement and the pathophysiology and diagnosis of different movement disorders. Some techniques can be accomplished in a routine clinical neurophysiology laboratory and others require some special equipment. This review, initiating a series of articles on this topic, focuses on the methods and techniques.

Exploring Interrater Disagreement on Essential Tremor Using a Standardized Tremor Elements Assessment.

Background: Patients with upper limb action tremor frequently exhibit additional neurological signs of uncertain significance. Clinicians vary in their interpretation, and interrater agreement on the final diagnosis is poor.

Objectives: A new clinical tool for assessing the presence or absence of clinical signs that are important in axis-1 classification of tremor patients is introduced: the Standardized Tremor Elements Assessment (STEA).

A Phase 2 Proof-of-Concept, Randomized, Placebo-Controlled Trial of CX-8998 in Essential Tremor.

Background: Available essential tremor (ET) therapies have limitations.

Objectives: The objective of this study was to evaluate CX-8998, a selective T-type calcium channel modulator, in essential tremor.

Methods: Patients 18-75 years old with moderate to severe essential tremor were randomized 1:1 to receive CX-8998 (titrated to 10 mg twice daily) or placebo.

Do We Belittle Essential Tremor by Calling It a Syndrome Rather Than a Disease? No.

A task force of the International Parkinson and Movement Disorder Society (MDS) recently published a tremor classification scheme that is based on the nosologic principle of two primary axes for classifying an illness: clinical manifestations (Axis 1) and etiology (Axis 2). An Axis 1 clinical syndrome is a recurring group of clinical symptoms, signs (physical findings), and possibly laboratory results that suggests the presence of at least one underlying Axis 2 etiology. Syndromes must be defined and used consistently to be of value in finding specific etiologies and effective treatments.

Development and Validation of the Orthostatic Tremor Severity and Disability Scale (OT-10).

Background: Limited tools are available for the assessment of orthostatic tremor severity and disability.

Objectives: To develop and validate a self-administered orthostatic tremor scale.

Methods: After expert consensus and literature review generating a list of 42 items, the scale was developed and modified for validation after a patient focus group, multiple rounds of Delphi panels, and cognitive interviews.

A Pilot Double-Blind Randomized Trial of Perampanel for Essential Tremor.

Background: Perampanel is a noncompetitive antagonist of alpha-amino-3-hydroxy-5-methylisoxazole propionic acid glutamate receptors suggested to modulate tremor.

Objectives: To assess the efficacy and tolerability of perampanel for essential tremor.

Methods: This was a double-blind, placebo-controlled, randomized, cross-over trial involving 26 patients titrated to 8 mg/day or a lower maximally tolerated dose as monotherapy or adjunct to antitremor medication.

Oculopalatal tremor following sequential medullary infarcts that did not cause hypertrophic olivary degeneration.

Background: The syndrome of oculopalatal tremor is a known consequence of lesions in the dentate-olivary pathway. Hypertrophic degeneration of the inferior olive is a recognized pathological correlate of these lesions and hypothesized to cause tremorogenic olivary hypersynchrony. However, oculopalatal tremor also occurs in Alexander disease, which produces severe inferior olive degeneration without intervening hypertrophy.

Temporal discrimination is altered in patients with isolated asymmetric and jerky upper limb tremor.

Background: Unilateral or very asymmetric upper limb tremors with a jerky appearance are poorly investigated. Their clinical classification is an unsolved problem because their classification as essential tremor versus dystonic tremor is uncertain. To avoid misclassification as essential tremor or premature classification as dystonic tremor, the term indeterminate tremor was suggested.

Estimating Change in Tremor Amplitude Using Clinical Ratings: Recommendations for Clinical Trials.

Tremor rating scales are the standard method for assessing tremor severity and clinical change due to treatment or disease progression. However, ratings and their changes are difficult to interpret without knowing the relationship between ratings and tremor amplitude (displacement or angular rotation), and the computation of percentage change in ratings relative to baseline is misleading because of the ordinal nature of these scales. For example, a reduction in tremor from rating 2 to rating 1 (0-4 scale) should not be interpreted as a 50% reduction in tremor amplitude, nor should a reduction in rating 4 to rating 3 be interpreted as a 25% reduction in tremor.

Current Opinions and Consensus for Studying Tremor in Animal Models.

Tremor is the most common movement disorder; however, we are just beginning to understand the brain circuitry that generates tremor. Various neuroimaging, neuropathological, and physiological studies in human tremor disorders have been performed to further our knowledge of tremor. But, the causal relationship between these observations and tremor is usually difficult to establish and detailed mechanisms are not sufficiently studied.

MDS evidence-based review of treatments for essential tremor.

Background: Essential tremor is one of the most prevalent movement disorders. Many treatments for essential tremor have been reported in clinical practice, but it is uncertain which options have the most robust evidence. The International Parkinson and Movement Disorder Society commissioned a task force on tremor to review clinical studies of treatments for essential tremor.

Comparison of the Fahn-Tolosa-Marin Clinical Rating Scale and the Essential Tremor Rating Assessment Scale.

Background: The Fahn-Tolosa-Marin Clinical Rating Scale for Tremor (FTM) has been used in large trials for essential tremor (ET), but its anchors for ratings from 0 to 4 of upper limb tremor are probably too low for patients with severe tremor (tremor amplitude >4 cm; grade 4). The Essential Tremor Rating Assessment Scale (TETRAS) is a validated clinical scale designed specifically for the assessment of ET severity. TETRAS has anchors that span a larger range of tremor amplitudes (>20 cm = grade 4), making it more suitable for assessing patients with severe ET.

Cerebello-cortical network fingerprints differ between essential, Parkinson's and mimicked tremors.

Cerebello-thalamo-cortical loops play a major role in the emergence of pathological tremors and voluntary rhythmic movements. It is unclear whether these loops differ anatomically or functionally in different types of tremor. We compared age- and sex-matched groups of patients with Parkinson's disease or essential tremor and healthy controls (n = 34 per group).

Surgical treatments for essential tremor.

Essential tremor is the most common form of pathologic tremor. Surgical therapies disrupt tremorogenic oscillation in the cerebellothalamocortical pathway and are capable of abolishing severe tremor that is refractory to available pharmacotherapies. Surgical methods are raspidly improving and are the subject of this review.