Milestones in Tremor Research: 10 Years Later

Abstract

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

Essential tremor plus rest tremor: current concepts and controversies

“…This calls for a standardization of the evaluation of RT in tremulous patients, to ensure comparability across different studies. Second, whereas we praise research efforts using imaging techniques to study the underpinnings of ET + RT, we admit that they only provide mechanistic evidence of which circuitry might be involved (Erro et al 2022 ), but essentially fail to provide any robust insights into the etiological correlates of this entity. The involvement of a specific circuitry might be shared by different disorders and, conversely, in a single disease multiple tremor types might be present as result of the involvement of different networks (Erro et al 2022 ).…”

“…Second, whereas we praise research efforts using imaging techniques to study the underpinnings of ET + RT, we admit that they only provide mechanistic evidence of which circuitry might be involved (Erro et al 2022 ), but essentially fail to provide any robust insights into the etiological correlates of this entity. The involvement of a specific circuitry might be shared by different disorders and, conversely, in a single disease multiple tremor types might be present as result of the involvement of different networks (Erro et al 2022 ). As such, future imaging research should attempt to adopt a multi-modal approach, including the use of DAT-SPECT, which is currently viewed as the gold standard for detecting dopaminergic dysfunction and against which to corroborate (or not) the results obtained by MRI.…”

A standardized accelerometry method for characterizing tremor: Application and validation in an ageing population with postural and action tremor

“…Ultimately, the abnormal tremor rhythms in ET implicate altered cerebello-thalamo-cortical-spinal circuits and can be suppressed using lesions in the motor thalamus ( Louis and Faust, 2020 ), or pharmacological modulation, including GABAergic or noradrenergic modulators ( Ferreira et al, 2019 ). Whether ET with its predominant postural and action tremor represents a distinct disease entity or is more a syndrome with heterogeneous etiology remains debated in the absence of large definitive clinicopathological correlative studies ( Erro et al, 2022 ). Systematic application of objective, standardized and readily applicable measures of tremor are required for better definition of the postural and action tremor spectrum, and ultimately more effective evaluation of new treatments.…”

“…In contrast to visual ordinal scales used by health care workers to qualitatively rate tremor severity and its impact on quality of life, power spectra derived from sensors provide more objective data with continuous variables ( Grimaldi and Manto, 2010 ; Elble and McNames, 2016 ). For example, power spectra of tremor derived from accelerometers may be useful for monitoring the progress of individual patients, and for evaluating the response of patient populations to drug therapies, deep brain stimulation, or other novel surgical therapies such as thalamic lesions using Magnetic Resonance Imaging guided Focused Ultrasound (MRgFUS) ( Duval et al, 2000 ; Nistico et al, 2016 ; van Brummelen et al, 2020 ; Cernera et al, 2021 ; Daneault et al, 2021 ; Erro et al, 2022 ).…”

“…A roadblock for the widespread use of the power spectrum in evaluation of tremor in clinical practice is the lack of reliable and standardized methods for acquisition and analysis. For example, results may vary with the anatomical site of transducer placement, type of sensor, whether acquisition is done in a structured clinical exam setting, duration of sampling, potential fluctuations during longer-term spontaneous recording, or variations in spectral analysis ( Mostile et al, 2012 ; Haubenberger et al, 2016 ; Schuhmayer et al, 2017 ; Erro et al, 2022 ). Here, we present a method that integrates accelerometry with a standardized clinical assessment protocol.…”