4.5 Review

Essential tremor: Clinical perspectives and pathophysiology

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Article Clinical Neurology

Increased Climbing Fiber Lateral Crossings on Purkinje Cell Dendrites in the Cerebellar Hemisphere in Essential Tremor

Yueh-Chi Wu et al.

Summary: This study found that patients with essential tremor have an increased number of climbing fiber crossings on Purkinje cell dendrites, potentially contributing to abnormal CF wiring and a positive correlation with tremor severity.

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Dentate Nucleus Neuronal Density: A Postmortem Study of Essential Tremor Versus Control Brains

Whitney G. Hartstone et al.

Summary: The study did not find significant differences in neuronal density or number in the dentate nucleus between essential tremor cases and controls.

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Non-invasive suppression of essential tremor via phase-locked disruption of its temporal coherence

Sebastian R. Schreglmann et al.

Summary: The study introduces a new method for real-time tracking of neural oscillations, which can be used to suppress aberrant neural oscillations associated with specific disorders, offering a new approach for the treatment of brain disorders.

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Features of ET plus correlate with age and tremor duration: ET plus may be a disease stage rather than a subtype of essential tremor

Elan D. Louis et al.

Summary: As patients with essential tremor (ET) age and the duration of tremor increases, they tend to develop more features of ET plus, which may represent a disease stage rather than a distinct subtype of the disease.

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Essential Tremor versus ET-plus: A Detailed Postmortem Study of Cerebellar Pathology

John T. Gionco et al.

Summary: This study found no significant pathological differences in cerebellar cortex between cases of ET and ET-plus, thus not supporting the idea that ET and ET-plus represent distinct clinical-pathological entities.

CEREBELLUM (2021)

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Directionality of corticomuscular coupling in essential tremor and cortical myoclonic tremor

S. Sharifi et al.

Summary: The study aimed to clarify the role of the motor cortex in tremor generation in essential tremor (ET) and familial cortical myoclonic tremor with epilepsy (FCMTE). The results showed that the majority of ET patients lacked a linear cortical drive, with weaker ascending coupling in ET compared to healthy controls around 5-6 Hz.

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

Spyros Papapetropoulos et al.

Summary: The study evaluated the efficacy of CX-8998 in essential tremor, showing some improvement in certain assessments despite not meeting the primary endpoint. Adverse events with CX-8998 included dizziness, headache, euphoric mood, and insomnia.

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The global prevalence of essential tremor, with emphasis on age and sex: A meta-analysis

Peige Song et al.

Summary: This study provides an up-to-date estimation of ET prevalence in the general population throughout the whole life span, with emphasis on age and sex. Future epidemiological investigations should adopt an internationally acknowledged diagnostic strategy.

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The diagnostic value of clinical neurophysiology in hyperkinetic movement disorders: A systematic review

S. van der Veen et al.

Summary: This article provides a systematic review on electrophysiological features used to differentiate between hyperkinetic movement disorders, focusing mainly on clinical tremor syndromes. Basic and task-related features in tremor syndromes overlap, but advanced signal analyses are more suited for specific types of tremor. Combinations of electrodiagnostic features are helpful in identifying different types of tremor.

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Purkinje cell axonal swellings enhance action potential fidelity and cerebellar function

Daneck Lang-Ouellette et al.

Summary: Axonal swellings on Purkinje cell axons in the cerebellum have been found during both healthy development and neurodegenerative diseases. Research shows that axons with swellings propagate action potentials more accurately, and young adult mice with more axonal swellings demonstrate better learning performance on cerebellar-related tasks.

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Imaging the Pathophysiology of Essential Tremor-A Systematic Review

Florian Holtbernd et al.

Summary: Functional imaging studies consistently show altered functional connectivity in the cerebellum and cerebello-thalamico-cortical circuitry. Structural imaging studies are less consistent, with no clear evidence for cerebellar neurodegeneration, but diffusion tensor imaging robustly points toward microstructural cerebellar changes.

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How Common is Essential Tremor? Update on the Worldwide Prevalence of Essential Tremor

Elan D. Louis et al.

Summary: The prevalence of essential tremor (ET) varies significantly across different regions globally, with higher prevalence among older age groups, especially those aged 65 and above. Gender does not impact the prevalence of ET.

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Essential tremor-plus: a controversial new concept

Elan D. Louis et al.

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Gene expression analysis of the cerebellar cortex in essential tremor

Regina T. Martuscello et al.

NEUROSCIENCE LETTERS (2020)

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Functional disconnection of the dentate nucleus in essential tremor

Sankalp Tikoo et al.

JOURNAL OF NEUROLOGY (2020)

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Essential tremor pathology: neurodegeneration and reorganization of neuronal connections

Elan D. Louis et al.

NATURE REVIEWS NEUROLOGY (2020)

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Excessive Cerebellar Oscillations in Essential Tremor: Insights Into Disease Mechanism and Treatment

Gerard Saranza et al.

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The Pathophysiology of Dystonic Tremors and Comparison With Essential Tremor

Pattamon Panyakaew et al.

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Molecular layer interneurons shape the spike activity of cerebellar Purkinje cells

Amanda M. Brown et al.

SCIENTIFIC REPORTS (2019)

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Etiologic links between environmental and lifestyle factors and Essential tremor

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Role of cerebellar GABAergic dysfunctions in the origins of essential tremor

Xu Zhang et al.

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Tremor Habituation to Deep Brain Stimulation: Underlying Mechanisms and Solutions

Alfonso Fasano et al.

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Whole genome sequencing and rare variant analysis in essential tremor families

Zagaa Odgerel et al.

PLOS ONE (2019)

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Reclassifying Essential Tremor: Implications for the Future of Past Research

Shweta Prasad et al.

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How to do an electrophysiological study of tremor

Felipe Vial et al.

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Tracking the central and peripheral origin of tremor

Ming-Kai Pan et al.

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The nature of postural tremor in Parkinson disease

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Climbing fiber-Purkinje cell synaptic pathology across essential tremor subtypes

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Resting-state fMRI study on drug-naive patients of essential tremor with and without head tremor

Ling Wang et al.

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Climbing fiber-Purkinje cell synaptic pathology in tremor and cerebellar degenerative diseases

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Stimulating at the right time: phase-specific deep brain stimulation

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Cerebellar Pathology in Early Onset and Late Onset Essential Tremor

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Hypertrophic Olivary Degeneration and Palatal or Oculopalatal Tremor

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Essential Tremor Is a Useful Concept? No

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Deep brain stimulation and climbing fiber synaptic pathology in essential tremor

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Early- and late-onset essential tremor patients represent clinically distinct subgroups

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A Randomized Trial of Focused Ultrasound Thalamotomy for Essential Tremor

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Ionic Basis for Membrane Potential Resonance in Neurons of the Inferior Olive

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Bilateral cerebellar activation in unilaterally challenged essential tremor

Marja Broersma et al.

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Essential and aging-related tremor: Differences of central control

Muthuraman Muthuraman et al.

MOVEMENT DISORDERS (2015)

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Rhythmic finger tapping reveals cerebellar dysfunction in essential tremor

A. W. G. Buijink et al.

PARKINSONISM & RELATED DISORDERS (2015)

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The nature of tremor circuits in parkinsonian and essential tremor

Hayriye Cagnan et al.

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Ultra-rapid axon-axon ephaptic inhibition of cerebellar Purkinje cells by the pinceau

Antonin Blot et al.

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Decreased EAAT2 protein expression in the essential tremor cerebellar cortex

Michelle Lee et al.

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Balance in essential tremor during tandem gait: Is the first mis-step an important finding?

N. Cinar et al.

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The inferior olivary nucleus: A postmortem study of essential tremor cases versus controls

Elan D. Louis et al.

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T-type channel blockade impairs long-term potentiation at the parallel fiber-Purkinje cell synapse and cerebellar learning

Romain Ly et al.

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Defective dentate nucleus GABA receptors in essential tremor

Sarah Paris-Robidas et al.

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Cortical magnetoencephalography of deep brain stimulation for the treatment of postural tremor

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Increased number of Purkinje cell dendritic swellings in essential tremor

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Increased number of heterotopic Purkinje cells in essential tremor

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Hairy Baskets'' Associated With Degenerative Purkinje Cell Changes in Essential Tremor

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Synchronized Brain Network Associated with Essential Tremor as Revealed by Magnetoencephalography

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Variant in the sequence of the LINGO1 gene confers risk of essential tremor

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Carbenoxolone and mefloquine suppress tremor in the harmaline mouse model of essential tremor

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LINGO-1 negatively regulates myelination by oligodendrocytes

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Genetic essential tremor in γ-aminobutyric acidA receptor α1 subunit knockout mice

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Selective disappearance of essential tremor after ischaemic stroke

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Characteristics of physiologic tremor in young and elderly adults

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Tremor-correlated cortical activity in essential tremor

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A comparison of continuous thalamic stimulation and thalamotomy for suppression of severe tremor.

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