Essential tremor

Welton, Thomas; Cardoso, Francisco; Carr, Jonathan; Chan, Ling‐Ling; Deuschl, G.; Jankovic, Joseph; Tan, Eng‐King

doi:10.1038/s41572-021-00314-w

Cited by 79 publications

(130 citation statements)

References 273 publications

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“…We previously demonstrated that electrical lesion of IO suppressed nicotine-induced tremor ( Kunisawa et al, 2016 ). Consistent with the fact that IO is closely involved in the pathogenesis of essential tremor in humans ( Puschmann and Wszolek, 2011 ; Kosmowska and Wardas, 2021 ; Welton et al, 2021 ), our results suggest that the IO-cerebellar system plays a crucial role in the generation of nicotine-induced kinetic tremor. IO receives dopaminergic innervation from the ventral tegmental and prerubral parafascicular areas ( Fallon et al, 1984 ; Toonen et al, 1998 ; Kitahama et al, 2000 ), suggesting a potential role of dopaminergic neurons in modulating tremor induction.…”

Section: Discussionsupporting

confidence: 89%

“…In addition, electrical lesion of IO suppressed the induction of nicotine tremor, illustrating that nicotine induces kinetic tremor by activating IO neurons. Since excitation of the olivo-cerebellar neural pathway is reportedly involved in generation of essential tremor in humans ( Puschmann and Wszolek, 2011 ; Kosmowska and Wardas, 2021 ; Welton et al, 2021 ), our findings suggest that nicotine-induced tremor has the same neural basis as essential tremor. In fact, nicotine tremor was significantly alleviated by drugs effective for human essential tremor (e.g., propranolol, diazepam, and phenobarbital), but was unaffected by medications for Parkinson’s disease tremor (i.e., trihexyphenidyl) ( Kunisawa et al, 2018 ).…”

Section: Introductionmentioning

confidence: 63%

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Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor

Kato

Kunisawa²,

Shimizu³

et al. 2022

Front. Pharmacol.

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Nicotine induces kinetic tremor, which resembles pharmacological features of essential tremors, via activating the inferior olive (IO) neurons. Since nicotine is known to enhance dopamine release by stimulating α4β2 and/or α6 nACh receptors, we examined the effects of various dopamine receptor ligands on nicotine-induced tremor to clarify the role of the dopaminergic system in modulating nicotine tremor. A tremorgenic dose of nicotine increased the dopamine level in the pons and medulla oblongata (P/MO), and the levels of dopamine metabolites in the hippocampus, P/MO, and striatum. Treatment of animals with the D1/5 agonist SKF-38393 inhibited the induction of nicotine tremor, whereas the D3 agonist PD-128,907 facilitated nicotine-induced tremor. The D2 agonist sumanirole showed no effect. In addition, nicotine tremor was significantly enhanced by the D1/5 antagonist SCH-23390 and inhibited by the D3 antagonist U-99194. Neither the D2 (L-741,626) nor D4 (L-745,870) antagonist affected the generation of nicotine tremor. Furthermore, microinjection of U-99194 into the cerebellum significantly inhibited nicotine-induced tremor, whereas its injection into IO or the striatum did not affect tremor generation. Although intrastriatal injection of SCH-23390 showed no effects, its injection into IO tended to enhance nicotine-induced tremor. The present study suggests that dopamine D3 and D1/5 receptors regulate the induction of nicotine tremor in an opposite way, D3 receptors facilitately and D1/5 receptors inhibitorily. In addition, the cerebellar D3 receptors may play an important role in modulating the induction of nicotine tremor mediated by the olivo-cerebellar system.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 63%

Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor

Kato

Kunisawa²,

Shimizu³

et al. 2022

Front. Pharmacol.

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“…Tremor as a clinical finding is commonly defined as a rhythmic shaking of a body part ( Clark and Louis, 2018 ; Welton et al, 2021 ). Involuntary tremor is generally composed of non-linear, non-stationary roughly sinusoidal oscillatory movements with a symmetric velocity profile about a theoretical midpoint ( Grimaldi and Manto, 2013 ; Deuschl et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…A wide variety of tremor syndromes can be distinguished by clinical history, associated neurological features, and involvement of different body parts. Physical examination of tremor at rest or with different postural or kinetic conditions allows for visual approximation of tremor frequency and amplitude, and is the mainstay for diagnosis and treatment follow-up ( Bhatia et al, 2018 ; Welton et al, 2021 ). Common pathological tremors include Essential Tremor (ET) (4–12 Hz), other types of cerebellum related tremors (2–10 Hz) including the irregular and lower frequency Holmes tremor (3–5 Hz), rest tremor typically seen in Parkinson’s disease (3–6 Hz), and the higher frequency orthostatic lower limb tremor (13–18 Hz) ( Grimaldi and Manto, 2013 ; Ondo et al, 2020 ; Deuschl et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…Essential Tremor (ET) is a common clinically diagnosed involuntary movement disorder with an estimated prevalence of 0.5% overall and 5% in people over age 65 ( Clark and Louis, 2018 ; Welton et al, 2021 ). ET can be sporadic or have a familial genetic component ( Welton et al, 2021 ). The frequency of postural limb tremor in ET varies between 4 and 12 Hz and is typically between 4 and 6 Hz.…”

Section: Introductionmentioning

confidence: 99%

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

Gauthier-Lafreniere

Aljassar

Rymar

et al. 2022

Front. Neuroinform.

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BackgroundOrdinal scales based on qualitative observation are the mainstay in the clinical assessment of tremor, but are limited by inter-rater reliability, measurement precision, range, and ceiling effects. Quantitative tremor evaluation is well-developed in research, but clinical application has lagged, in part due to cumbersome mathematical application and lack of established standards.ObjectivesTo develop a novel method for evaluating tremor that integrates a standardized clinical exam, wrist-watch accelerometers, and a software framework for data analysis that does not require advanced mathematical or computing skills. The utility of the method was tested in a sequential cohort of patients with predominant postural and action tremor presenting to a specialized surgical clinic with the presumptive diagnosis of Essential Tremor (ET).MethodsWristwatch accelerometry was integrated with a standardized clinical exam. A MATLAB application was developed for automated data analysis and graphical representation of tremor. Measures from the power spectrum of acceleration of tremor in different upper limb postures were derived in 25 consecutive patients. The linear results from accelerometry were correlated with the commonly used non-linear Clinical Rating Scale for Tremor (CRST).ResultsThe acceleration power spectrum was reliably produced in all consecutive patients. Tremor frequency was stable in different postures and across patients. Both total and peak power of acceleration during postural conditions correlated well with the CRST. The standardized clinical examination with integrated accelerometry measures was therefore effective at characterizing tremor in a population with predominant postural and action tremor. The protocol is also illustrated on repeated measures in an ET patient who underwent Magnetic Resonance-Guided Focused Ultrasound thalamotomy.ConclusionQuantitative assessment of tremor as a continuous variable using wristwatch accelerometry is readily applicable as a clinical tool when integrated with a standardized clinical exam and a user-friendly software framework for analysis. The method is validated for patients with predominant postural and action tremor, and can be adopted for characterizing tremor of different etiologies with dissemination in a wide variety of clinical and research contexts in ageing populations.

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Alteration of White Matter Connectivity for MR‐Guided Focused Ultrasound in the Treatment of Essential Tremor

Wang

Lin

et al. 2023

Magnetic Resonance Imaging

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BackgroundMagnetic resonance‐guided focused ultrasound (MRgFUS) thalamotomy has been implemented as a therapeutic alternative for the treatment of drug‐refractory essential tremor (ET). However, its impact on the brain structural network is still unclear.PurposeTo investigate both global and local alterations of the white matter (WM) connectivity network in ET after MRgFUS thalamotomy.Study TypeRetrospective.SubjectsTwenty‐seven ET patients (61 ± 11 years, 19 males) with MRgFUS thalamotomy and 28 healthy controls (HC) (61 ± 11 years, 20 males) were recruited for comparison.Field Strength/SequenceA 3 T/single shell diffusion tensor imaging by using spin‐echo‐based echo‐planar imaging, three‐dimensional T1 weighted imaging by using gradient‐echo‐based sequence.AssessmentPatients were undergoing MRgFUS thalamotomy and their clinical data were collected from pre‐operation to 6‐month post‐operation. Network topological metrics, including rich‐club organization, small‐world, and efficiency properties were calculated. Correlation between the topological metrics and tremor scores in ET groups was also calculated to assess the role of neural remodeling in the brain.Statistical TestsTwo‐sample independent t‐tests, chi‐squared test, ANOVA, Bonferroni test, and Spearman's correlation. Statistical significance was set at P < 0.05.ResultsFor ET patients, the strength of rich‐club connection and clustering coefficient significantly increased vs. characteristic path length decreased at 6‐month post‐operation compared with pre‐operation. The distribution pattern of rich‐club regions was different in ET groups. Specifically, the order of the rich‐club regions was changed according to the network degree value after MRgFUS thalamotomy. Moreover, the altered nodal efficiency in the right temporal pole of the superior temporal gyrus (R = 0.434–0.596) and right putamen (R = 0.413–0.436) was positively correlated with different tremor improvement.Data ConclusionThese findings might improve understanding of treatment‐induced modulation from a network perspective and may work as an objective marker in the assessment of ET tremor control with MRgFUS thalamotomy.Level of Evidence3Technical EfficacyStage 4

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Essential tremor

Cited by 79 publications

References 273 publications

Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor

Mechanisms Underlying Dopaminergic Regulation of Nicotine-Induced Kinetic Tremor

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

Alteration of White Matter Connectivity for MR‐Guided Focused Ultrasound in the Treatment of Essential Tremor

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