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Tremor is the most frequent human movement disorder, and its diagnosis is based on clinical assessment. Yet finding the accurate clinical diagnosis is not always straightforward. Fine-tuning of clinical diagnostic criteria over the past few decades, as well as device-based qualitative analysis, has resulted in incremental improvements to diagnostic accuracy. Accelerometric assessments are commonplace, enabling clinicians to capture high-resolution oscillatory properties of tremor, which recently have been the focus of various machine-learning (ML) studies. In this context, the application of ML models to accelerometric recordings provides the potential for less-biased classification and quantification of tremor disorders. However, if implemented incorrectly, ML can result in spurious or nongeneralizable results and misguided conclusions. This work summarizes and highlights recent developments in ML tools for tremor research, with a focus on supervised ML. We aim to highlight the opportunities and limitations of such approaches and provide future directions while simultaneously guiding the reader through the process of applying ML to analyze tremor data. We identify the need for the movement disorder community to take a more proactive role in the application of these novel analytical technologies, which so far have been predominantly pursued by the engineering and data analysis field. Ultimately, big-data approaches offer the possibility to identify generalizable patterns but warrant meaningful translation into clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

For nearly a century, functional neurosurgery has been applied in the treatment of tremor. While deep brain stimulation has been in the focus of academic interest in recent years, the establishment of incisionless technology, such as MRI-guided high-intensity focused ultrasound, has again stirred interest in lesional approaches.In this article, we will discuss the historical development of surgical technique and targets, as well as the technological state-of-the-art of conventional and incisionless interventions for tremor due to Parkinson's disease, essential and dystonic tremor and tremor related to multiple sclerosis (MS) and midbrain lesions. We will also summarise technique-inherent advantages of each technology and compare their lesion characteristics. From this, we identify gaps in the current literature and derive future directions for functional lesional neurosurgery, in particularly potential trial designs, alternative targets and the unsolved problem of bilateral lesional treatment. The results of a systematic review and meta-analysis of the consistency, efficacy and side effect rate of lesional treatments for tremor are presented separately alongside this article., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: This work evaluates the consistency, effect size and incidence of persistent side effects of lesional neurosurgical interventions in the treatment of tremor due to Parkinson's disease (PD), essential tremor (ET), multiple sclerosis (MS) and midbrain lesions., Methods: Systematic review and meta-analysis according to PRISMA-P guidelines. Random effects meta-analysis of standardised mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049)., Results: From 1249 abstracts screened, 86 peer-reviewed studies reporting 102 cohorts homogeneous for tremor aetiology, surgical target and technique were included.Effect on PD tremor was better when targeted at the ventral intermediate nucleus (V.im.) by radiofrequency ablation (RF) (Hedge's g: -4.15;) over V.im. by Gamma Knife (GK) (-2.2), subthalamic nucleus (STN) by RF (-1.12) and globus pallidus internus (GPi) by RF (-0.89). For ET MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (-2.35) and V.im. (-2.08) showed similar mean tremor reductions to V.im. ablation by RF (-2.42) or GK (-2.13). In MS V.im. ablation by GK (-1.96) and RF (-1.63) were similarly effective.Mean rates of persistent side effects after unilateral lesions in PD were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0% (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7% (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral tremor 30.3% (RF V.im.)., Conclusion: This meta-analysis quantifies safety, consistency and efficacy of lesional neurosurgical interventions for tremor by target, technique and aetiology., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: The development of high-intensity magnetic resonance imaging (MRI)-guided focused ultrasound (MRIgFUS) ablation has widened the spectrum of interventional techniques for stereotactic functional neurosurgery of lesions. This has resulted in novel incisionless intervention approaches for the therapy of tremor disorders. The safety and efficacy is documented by recent study data., Objectives: This article encompasses a description of the technological basis and typical course of MRIgFUS interventions, a comparison to alternative open or incisionless surgical techniques as well as a review of the current evidence base for MRIgFUS ablation in the context of lesional interventions to treat tremor., Material and Methods: Narrative literature review and comparison., Results: Depending on the surgical target and tremor etiology published trials of MRIgFUS ablation report a reduction of tremor intensity of up to 80% after 6-12 months follow-up without the disadvantages of open brain surgery., Conclusion: The MRIgFUS functional neurosurgery is conducted only at a limited number of treatment sites. First data on lesions of the thalamic ventral intermediary nucleus (V.im.) as well as subthalamic fiber tracts have been published. These results indicate an effective and safe treatment of tremor disorders by MRIgFUS ablation. Incisionless lesional surgery using MRIgFUS is a significant addition to the interventional armamentarium for functional stereotactic neurosurgery and a potentially valuable alternative to established interventional therapy options for tremor disorders.

Introduction: The recent introduction of incision-less lesional neurosurgery using Gamma Knife and MRI-guided focused ultrasound has revived interest in lesional treatment options for tremor disorders. Preliminary literature researches reveal that the consistency of treatment effects after lesional neurosurgery for tremor has not formally been assessed yet. Similarly, the efficacy of different targets for lesional treatment and incidence of persistent side effects of lesional neurosurgical interventions has not been comprehensively assessed. This work therefore aims to describe a suitable process how to review the existing literature on efficacy and persistent side effects of lesional neurosurgical treatment for tremor due to Parkinson's disease, essential tremor, multiple sclerosis and midbrain/rubral tremor., Methods and Analysis: We will search electronic databases (Medline, Cochrane) and reference lists of included articles for studies reporting lesional interventions for tremor in cohorts homogeneous for tremor aetiology and intervention (technique and target). We will include cohorts with a minimum number of five subjects and follow-up of 2 months. One investigator will perform the initial literature search and two investigators then independently decide which references to include for final efficacy and safety analysis. After settling of disagreement, data will be extracted from articles using a standardised template. We will perform a random-effect meta-analysis calculating standardised mean differences (Hedge's g) for comparison in Forest plots and subgroup analysis after assessment of heterogeneity using I 2 statistics., Ethics and Dissemination: This study will summarise the available evidence on the efficacy of lesional interventions for the most frequent tremor disorders, as well as for the incidence rate of persisting side effects after unilateral lesional treatment. This data will be useful to guide future work on incision-less lesional interventions for tremor., Systematic Review Registration: This study has been registered with the PROSPERO database (no. CRD42016048049)., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Diagnosis and treatment of tremor are largely based on clinical assessment. Whereas in some patients tremor may respond to dopaminergic treatment, in general l-Dopa response to tremor varies considerably. The aim of this study was to predict l-Dopa response by accelerometry., Methods: We included 60 tremor patients and measured harmonic oscillations by accelerometry. In addition to neurological assessment, we performed l-Dopa challenge tests and the individual tremor response was compared to the amount of harmonic oscillations., Results: We found a strong correlation between harmonic oscillations and clinical l-Dopa response. Similarly, harmonic oscillations were significantly greater in patients with subjective tremor reduction upon l-Dopa administration., Conclusions: We conclude that harmonic oscillations are a measure for l-Dopa response to tremor irrespective of the underlying disease. Because of the observational character of the study, any causal relation remains speculative. Nevertheless, we propose a novel, non-invasive approach to predict l-Dopa response in tremor patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)