Evidence map›Paper›PMID 41445625›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Natural disease progression vs. DBS-related worsening in essential tremor.

Nisrine Bakri, Adolfo Ramirez-Zamora, Michael S Okun, Kelly Foote, Evangelos Christou, Karim Oweiss

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Nisrine BakriDepartment of Electrical and Computer Engineering, University of Florida, Gainesville, FL, USA.ORCID 0009-0008-0172-0540
Adolfo Ramirez-ZamoraNeurology, University of Florida, Gainesville, FL, USA.ORCID 0000-0001-9253-3899
Michael S OkunNeurology, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-6247-9358
Kelly FooteNeurosurgery, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-2436-4138
Evangelos ChristouApplied Physiology and Kinesiology, University of Florida, Gainesville, FL, USA.
Karim OweissDepartment of Electrical and Computer Engineering, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-1175-7258

Funding

Dual Lead Thalamic DBR-DBS Interface for Closed Loop Control of Severe Essential TremorUH3NS109845 · NINDS · UNIVERSITY OF FLORIDA · PI FOOTE, KELLY D, OWEISS, KARIM G · 2019 to 2025
$3.6M
NINDS NIH HHS UH3 NS109845
6 · The paper itself

Abstract

Essential tremor is a disabling and highly prevalent movement disorder. Deep brain stimulation of the ventral intermediate nucleus provides substantial symptom relief; however, many patients experience diminishing benefit over time. The underlying causes range from natural disease progression and worsening ataxia to, less commonly, habituation or tolerance. We performed a retrospective longitudinal analysis of 86 individuals with essential tremor who underwent unilateral ventral intermediate nucleus deep brain stimulation and had three or more follow-up visits (mean follow-up duration 5.2 years; maximum 15.4 years; >470 total visits). This approach provided a unique opportunity to assess contralateral limbs in addition to long term effects of stimulation. Tremor severity was quantified using the Fahn-Tolosa-Marin Tremor Rating Scale total score and subscores, with particular focus on contralateral and ipsilateral upper-extremity tremor. Longitudinal trajectories were assessed across limbs and stimulation states at both the population and individual levels. Comparison of tremor between the non-stimulated side and the stimulated side were conducted in the stimulation off condition and served as an intrinsic control to disentangle natural disease progression from tolerance to deep brain stimulation. Contralateral and ipsilateral upper-extremity tremor assessed with stimulation off showed slow, bilateral progression over time. Tremor in the ipsilateral limb followed the same trajectory as the unstimulated contralateral limb, consistent with natural disease progression. Stimulation exerted no measurable cross-hemispheric influence, as ipsilateral tremor progressed similarly with stimulation on and off. During chronic stimulation, tremor progression in the stimulated limb closely tracked that of the ipsilateral limb, with most patients showing no meaningful difference between sides. Progression in the stimulated limb was also similar during stimulation on and off conditions, suggesting that habituation, stimulation-induced maladaptation, or deep brain stimulation-accelerated decline was not observed in this cohort. Long-term symptoms of worsening tremor in essential tremor patients with unilateral ventral intermediate nucleus deep brain stimulation were primarily driven by natural disease progression, not by deep brain stimulation-related causes. While tolerance may rarely emerge, the dominant effect of worsening is disease progression. In this cohort, the stimulation programming parameters were individually optimised over time, likely minimizing the influence of suboptimal programming or stimulation-related decline. These findings underscore the importance of extended comprehensive outcome assessment in essential tremor, incorporating objective measures to distinguish disease progression from treatment-related effects. Follow-up studies are needed to better characterise the relative contributions of tremor and ataxia to long-term disability.

Indexed as

deep brain stimulationdisease progressionessential tremorstimulation habituationthalamustremor rating scale

Identifiers

PMID41445625
PMCPMC12724148

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.