A prospective controlled study of a wearable rhythmic vibrotactile device for tremor in Parkinson’s disease

Clinical Neurophysiology, Journal Year: 2025, Volume and Issue: 172, P. 51 - 60

Published: Feb. 8, 2025

Tremor in Parkinson's disease (PD) does not always respond to dopaminergic medication, therefore new treatment strategies are needed. Preliminary evidence has suggested that manipulation of peripheral afferents may reduce tremor amplitude, but existing research is inconclusive and been properly controlled. Here, we explored the effects vibrotactile stimulation (ViS) on PD using a within-subjects controlled design. Thirty patients with clear were included. ViS (open-loop) was applied most affected wrist. Four conditions compared: frequency (TF), 1.5*TF, 80 Hz stimulation, sham. We tested effect these power (measured accelerometry) during three contexts: rest tremor, cognitive load, postural tremor. Entrainment between complex phase-locking value (PLV). There no significant when applied. Stimulation did depend context which occurred. PLVs showed phase influenced by ViS. Open-loop modulate This study one first large sample studies investigate how influence objective measures PD.

Language: Английский

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Milestones in Tremor Research: 10 Years Later

Movement Disorders Clinical Practice, Journal Year: 2022, Volume and Issue: 9(4), P. 429 - 435

Published: Feb. 3, 2022

Major progress has occurred during the last decade in field of tremor. From clinical standpoint, a new classification completely revised nosology tremor syndromes and re-conceptualized essential as syndrome rather than single disease entity, fueling an ongoing enlightened debate. Significant advances have been obtained terms instrumental measurement tremor, remarking on possibility developing novel treatment strategies based characteristics, namely tremor-phase. Moreover, better understanding pathophysiological mechanisms further led to suggestion refining according their driving underpinnings. Finally, surgical options such deep brain stimulation focused ultrasound thalamotomy are now part therapeutic portfolio for but several oral drugs, including long-chain alcohols, T-channel blockers, allosteric modulators potassium channels, GABA-A receptors, currently being tested hold promise. This review will discuss key milestones research 10 years, with focus most common syndromes, dystonic Parkinsonian

Language: Английский

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

Movement Disorders Clinical Practice, Journal Year: 2024, Volume and Issue: 11(6), P. 645 - 654

Published: April 9, 2024

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

Language: Английский

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Connecting tremors – a circuits perspective

Current Opinion in Neurology, Journal Year: 2022, Volume and Issue: 35(4), P. 518 - 524

Published: July 5, 2022

Purpose of review Tremor is one the most prevalent movement disorders in clinical practice. Here, we new insights pathophysiology tremor. We focus on three common tremor disorders: essential (ET), dystonic syndrome (DTS), and Parkinson's disease (PD) Recent findings Converging evidence suggests that ET, DTS, PD are all associated with (partly) overlapping cerebral networks involving basal ganglia cerebello-thalamo-cortical circuit. studies have assessed role these by measuring tremor-related activity connectivity electrophysiology neuroimaging, perturbing network components using invasive noninvasive brain stimulation. The cerebellum plays a more dominant causal action tremors than rest tremor, as exemplified recent re-emergent PD. Furthermore, DTS related to differences between patients, for example, whether or not occurs limb, jerky sinusoidal. Summary Insight into pathophysiological mechanisms may provide direct window mechanism-based treatment options either etiology phenotype syndrome.

Language: Английский

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The Pathophysiology of Tremor

Cambridge University Press eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 499 - 512

Published: Jan. 7, 2025

Language: Английский

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Between Nothing and Everything: Phenomenology in Movement Disorders

Movement Disorders, Journal Year: 2023, Volume and Issue: 38(10), P. 1767 - 1773

Published: Sept. 21, 2023

In movement disorders, phenomenology refers to the science and art of classifying abnormal movements. Traditional clinical practice has been based on phenotype-driven investigation, diagnosis, management. However, many have questioned our continued reliance phenotype. Phenotype repeatedly demonstrated be an unreliable guide precise lower-level pathophysiological process. After all, a single phenotype can caused by multiple diseases genetic disorder associated with varied phenotypes. There growing call for molecular subtyping priority in scientific research. this Viewpoint, we redebate relevance phenotype, arguing that may using wrong way. We discuss how better appreciation many-diseases-to-few-phenotypes process allow experimental literature more effectively understood. suggest convergence onto limited number phenotypic patterns reflect fact sensorimotor system only "break" ways. Therefore, if understand system-level processes underpin specific phenotypes, could unlock novel phenotype-specific therapies regardless underlying disease Encouragingly, existing therapeutic tools such as neuromodulation already target processes. The term (from Greek ϕαινο-, (faino-), "showing," τύπος, (túpos), "type") observable physical properties organism.1, 2 These include organism's appearance, development, behavior are determined interactions between genetic, environmental, stochastic factors.3 is generally used label category derived from examination observation patient. Bradykinesia,4 chorea,5 dystonia,6 myoclonus,7 tics,5 tremor8 make up major categories descriptive definitions capture essence each (Fig. 1).9 This categorization vital part formulation disorders classic textbooks organized differential diagnosis treatment selection.10 often dictates group patients research trials evaluate success interventions through use severity scores.11-14 A neurologist training develops skill identifying correctly subclassifying experience supervision specialists disorders. pattern recognition task imperfect subjective. When subtle, labeling become dependent personal thresholds when "call" particular present. relative preservation classification generations suggests convey something meaningful. Often or distribution nuances individual, but overriding core usually clear. consistent architecture defines behavioral features neurodegenerative conditions, different stages For example, early Huntington's choreiform movements typical, whereas later Parkinsonian commonly seen. therefore appears responsive evolving dysfunction accumulating neurodegeneration. non-degenerative stable: once nervous failed way, it does not change. Historically, astute phenotyping was main point access pathophysiology foundation clinico-pathological method. now know mapping phenotypes.15 Our current groupings hugely useful guiding do precisely reveal etiology. driven which develop therapeutics strategies important should welcomed.15 mean abandon interest Instead, need reasons why there disconnect disconnect. where biologically fundamental concept degeneracy useful. word context meaning familiar describe cellular degeneration diseases. defined "the ability elements structurally perform same function yield output."16 Describing many-to-one distinct redundancy occurs performed identical elements.17 Degeneracy ubiquitous properly biological systems at all levels organization.16 code degenerate codons (nucleotide triplets) specifying amino acid.18 Even simple organisms (such crustacean stomatogastric ganglion 26 neurones), similar network performance arise diverse combinations neuronal activity.19-23 thought improve resilience damage key mechanism adaptability drives natural selection.24 collapsing few common mapping, example architecture. repercussions both clinically experimentally. interested readers, supplemental material article simulates might affect interpretation data ways (Supplementary Fig.). Indeed, very reasonable criticisms distilled down failure appreciate importance degeneracy.9 give illness primacy studies "gold standard" categorical variable. means constrain bias analysis assumption participants study because they share characteristics. Experimental markers will continue mislead interchangably (specific disease) higher-level (common phenotype) (Fig., Supplementary Furthermore, implies unbroken chain causality any measure population way typically described publications demonstrates Krakaeur et al. detail various examples "filler verbs" effect papers ("underlies," "produces," "mediates," "plays role in," "reflects," "encodes," "regulates.")25 Research imply observe change variable directly related mechanistically relevant fashion leads inevitable conclusion normalizing quality life tells us incorrect changes marker lower causally generation. break legacy neurology considered window opening linked highly complex manner disease-level dysfunction. To reach fuller understanding able explain dysfunctions organisation. Each level investigation conceptual needed rules underwriting one investigates depend question being asked.25, Interestingly, organization independence complete explanatory power higher-order 2B). Correspondingly, characterization machinery responsible knowledge breaks cause also ramifications those trying animal models due differences human other brains. optimal approach investigate vary. some beginning methods allows try reverse causal deficit. pragmatic reality curative, affordable remain distant prospect.27, 28 involves interplay factors, pure "fix" never available. still great forms build alternative system. Clinical relatively invariant stable types "system failure" observed behavior. One parameters underwrite production recognizing disease. If take tremor "easiest" reliably identify extract oscillatory Such characterize defining activity cortico-cerebello-thalamo-cortical network.30, 31 treat origin, lesions deep brain stimulation (DBS) surgery, (almost) causing tremor. phenotypes underwritten neural dynamics within brain. Advances technology motion dynamically over time. This, closely actual reflecting coordinated function, most likely underwrites signatures then Most simply, quantification help objectively monitor Reliable quantitative biomarkers feed back into interventions, feature minimized adaptive DBS. Scientifically, dynamic statistics powerfully paired techniques continuous neurophysiological recordings correlate process, refining mechanisms. information hopefully further range patterns. stability controller difficult, without intervention, claw normal motor control. conceptualize these observations consider state 3A). favorable response DBS possible move state. returning circuit healthier require reversal It practical find new improves rather than undo component accumulated 3B).32 converge makes its corresponding obvious development. reduces problem list orders magnitude thousands fewer prioritising fits anticipated landscape viable therapies. looking define mode design-targeted neurophysiotherapy, equip design 2C). approaches enticing, "closer" manifestations predictable symptomatic contrasts variables function.33 Currently, imprecisely defined. Interrater reliability low witnessed debates two about whether predominantly "phenotype A" versus B." As case frank disagreement, "partially" true, is, overlapping distributions certain across categories. By moving towards objective what quanta dysfunctional relevant. meaningful, subcategories branch With sample extended time periods naturalistic everyday settings huge expansion amount nature available categorization. Data-led governed statistical factors hidden clinician-led recognition. divisions were first carved out. community create validate movement, rooted their utility and/or shed light mechanism, evolve outcomes. discrete displayed viewed opportunity. itself, greater efficacy end goal bridge levels. until broader scope organizational levels, hierarchical independence, difficult headway aim. Using multipronged fruitful accelerate discovery axes drive innovation. advocate focus discovery. thank John Rothwell invaluable critical discussion manuscript. (1) Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: Design, Execution, Review Critique; (3) Manuscript Preparation: Writing First Draft, Critique. A.S.: 3A, 3B. M.J.E.: Not applicable Data S1. Supporting Please note: publisher content functionality supporting supplied authors. Any queries (other missing content) directed author article.

Language: Английский

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The Cerebellum and the Motor Cortex: Multiple Networks Controlling Multiple Aspects of Behavior

The Neuroscientist, Journal Year: 2023, Volume and Issue: 30(6), P. 723 - 743

Published: Aug. 31, 2023

The cerebellum and its thalamic projections to the primary motor cortex (M1) are well known play an essential role in executing daily actions. Anatomic investigations animals postmortem humans have established reciprocal connections between these regions; however, how pathways can shape cortical activity behavioral contexts help promote recovery neuropathological conditions remains not understood. present review aims provide a comprehensive description of discuss novel noninvasive brain stimulation (NIBS) methods be used gain deeper understanding cerebellar-M1 connections. In first section, we focus on recent animal literature that details information sent from thalamus is integrated into broad network neurons. We then NIBS approaches reliably assess connectivity M1. Moreover, latest perspectives using advanced investigate modulate multiple cerebellar-cortical networks involved movement behavior plasticity. Finally, emerging been translation research produce long-lasting modifications cerebellar-thalamic-M1 restore function neurologic patients.

Language: Английский

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Clinical neurophysiology in the treatment of movement disorders: IFCN handbook chapter

Clinical Neurophysiology, Journal Year: 2024, Volume and Issue: 164, P. 57 - 99

Published: May 23, 2024

In this review, different aspects of the use clinical neurophysiology techniques for treatment movement disorders are addressed. First all, these can be used to guide neuromodulation or perform therapeutic as such. Neuromodulation includes invasive based on surgical implantation electrodes and a pulse generator, such deep brain stimulation (DBS) spinal cord (SCS) one hand, non-invasive aimed at modulating even lesioning neural structures by transcranial application. Movement main areas indication various techniques. This review focuses following techniques: DBS, repetitive magnetic (rTMS), low-intensity electrical stimulation, including direct current (tDCS) alternating (tACS), focused ultrasound (FUS), high-intensity resonance-guided FUS (MRgFUS), pulsed mode (TUS). The conditions in which has proven its efficacy Parkinson's disease, dystonia, essential tremor, mainly using DBS MRgFUS. There is also some evidence Tourette syndrome (DBS), Huntington's disease cerebellar ataxia (tDCS), axial signs depression (rTMS) PD. development limited short-term impact techniques, especially rTMS, context very chronic diseases. However, at-home advances design closed-loop (tACS) may open new perspectives application patients, favored their easier lower rate adverse effects compared methods. Finally, summarizes keeping electromyography optimize identification muscles treated with botulinum toxin injection, indicated widely performed disorders.

Language: Английский

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Cerebellar Transcranial Alternating Current Stimulation in Essential Tremor Patients with Thalamic Stimulation: A Proof-of-Concept Study

Neurotherapeutics, Journal Year: 2023, Volume and Issue: 20(4), P. 1109 - 1119

Published: April 25, 2023

Language: Английский

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Phenotypical differentiation of tremor using time series feature extraction and machine learning

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 15, 2024

Abstract The reliable differentiation of tremor disorders poses a significant challenge, largely depending on the subjective interpretation subtle signs and symptoms. Given absence universally accepted bio-marker, diagnostic between most prevalent disorders, Essential Tremor (ET) tremor-dominant Parkinson’s Disease (PD), frequently proves to be non-trivial task. To address this, we employed massive time series feature extraction, powerful tool examine entirety mathematical descriptors oscillating biological signals without imposing bias, in combination with machine-learning (ML). We applied this approach accelerometer recordings from patients identify optimal recording conditions, processing, analysis settings, differentiate ET PD. utilized hand 370 (167 ET, 203 PD), clinically diagnosed at five academic centres specialising movement comprising an exploratory (158 172 PD London, Graz, Budapest, Kiel) validation dataset (9 31 Nijmegen). Using 15 second segments more affected hand, first extracted established, standardized characteristics assessed their cross-centre accuracy validity. Second, supervised ML higher-order extraction same achieve stratification mechanistic exploration. While classic were unable consistently conditions across centres, resulting best classifying validated successfully. In comparison tremor-stability index (TSI), performing characteristic, feature-based provided better classification (81.8% vs. 70.4%), sensitivity (86.4% 70.8%) specificity (76.6% 70.2%), substantially improving tremor. Similarly, allowed rest posture independent diagnosis, again outperforming TSI (classification 99.6% 49.2%). identified features indicates fundamentally different dynamics generating circuits: while there is interaction several central oscillators generation tremor, discrete but stable signal states, point towards singular pacemaker ET. This study highlights limitations current, established metrics establishes use machine learning as method explore accelerometry-derived characteristics. More importantly, it showcases strength hypothesis-free, data-driven analyses large, multi-centre dataset. results generated are thus resistant device-, centre- clinician-dependent bias establish generalizable method, representing relevant step big data disorders.

Language: Английский

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