Deep brain stimulation for essential tremor [Neurosurgery Wiki]

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====== Deep brain stimulation for essential tremor ======

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With technological advances, [[deep brain stimulation]] (DBS) to the [[VIM]] has replaced [[thalamotomy]] as the operation of choice for patients with [[essential tremor]]s, given the heightened risk of permanent [[neurological deficit]]s associated with ablative surgery. Multiple studies have demonstrated that unilateral VIM DBS has significant short- and long-term benefits for targeted tremors. Unilateral VIM DBS may also improve head and [[voice tremor]], although most commonly bilateral stimulation is required for adequate control. However, bilateral thalamic stimulation is associated with a higher incidence of neurological deficits, particularly [[speech]] and [[gait]] problems. Investigations of DBS of other brain target areas for essential tremors, such as the [[posterior subthalamic area]] and the [[subthalamic nucleus]], are ongoing
((Nazzaro JM, Lyons KE, Pahwa R. Deep brain stimulation for essential tremor. Handb Clin Neurol. 2013;116:155-66. doi: 10.1016/B978-0-444-53497-2.00013-9. PMID: 24112892.)).
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[[Deep brain stimulation]] (DBS) in thalamic ventrointermediate ([[VIM]]) nucleus is the traditional target for the surgical treatment of pharmacologically refractory [[essential tremor]] (ET) or parkinsonian tremor.

The [[Food and Drug Administration]] (FDA) approved [[DBS]] as a treatment for [[essential tremor]] in [[1997]].

===== Target =====

Still, the optimal anatomical target in the [[subthalamic]] area is a matter of debate. The aim of a study of Kübler et al. was to determine the optimal target of DBS for [[essential tremor]] regarding beneficial [[clinical outcome]] and impact on activities of daily living as well as [[stimulation]]-induced side effects and compare it with previously published coordinates.

In 30 ET patients undergoing bilateral DBS, the severity of tremor was assessed by blinded video ratings before and at 1-year follow-up with DBS ON and OFF. Tremor scores and reported side effects and volumes of tissue activated were used to create a probabilistic map of DBS efficiency and side effects.

DBS was effective both in tremor suppression as well as in improving patient-reported outcomes, which were positively correlated. The "sweet spot" for tremor suppression was located inferior to the VIM in the subthalamic area, close to the superior margin of the zona incerta. The Euclidean distance of active contacts to this spot as well as to 10 of 13 spots from the literature review was predictive of individual outcome. A cluster associated with the occurrence of ataxia was located in the direct vicinity of the "sweet spot".

The findings suggest the highest clinical efficacy of DBS in the [[posterior subthalamic area]], lining up with previously published targets likely representing the [[dentato-rubro-thalamic tract]]. Side effects may not necessarily indicate lead misplacement but should encourage clinicians to employ novel DBS programming options
((Kübler D, Kroneberg D, Al-Fatly B, Schneider GH, Ewert S, van Riesen C, Gruber D, Ebersbach G, Kühn AA. Determining an efficient deep brain stimulation target in essential tremor - Cohort study and review of the literature. Parkinsonism Relat Disord. 2021 Jun 29;89:54-62. doi: 10.1016/j.parkreldis.2021.06.019. Epub ahead of print. PMID: 34225135.)).
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Patients with ET treated with [[deep brain stimulation]] (DBS) with stimulation-induced dysarthria (SID), individualized  current-shaping with [[interleaving stimulation]] (cs-ILS) reduces dysarthria while maintaining [[tremor]] control ((Barbe MT, Dembek TA, Becker J, Raethjen J, Hartinger M, Meister IG, Runge M,
Maarouf M, Fink GR, Timmermann L. Individualized current-shaping reduces
DBS-induced dysarthria in patients with essential tremor. Neurology. 2014 Jan 17.
[Epub ahead of print] PubMed PMID: 24443448.)).

===== Complications =====

Long-term hardware complications include equipment malfunction, skin erosion, and battery replacements, which require additional surgery
((Lyons KE, Pahwa R. Deep brain stimulation and essential tremor. J Clin Neurophysiol. 2004 Jan-Feb;21(1):2-5. doi: 10.1097/00004691-200401000-00002. PMID: 15097289.)).

===== Clinical trials =====

There is little evidence regarding the possible [[neuropsychological]] effects of [[posterior subthalamic area]]-DBS on patients with ET, and there are few studies comparing it with [[VIM]]-DBS in this population.In this study, Triguero-Cueva et al. aim to present the evaluation [[protocol]] and [[neuropsychological battery]] as used in an ongoing trial of DBS for ET comparing the already mentioned targets.

As part of a randomized, [[double-blind]], [[crossover]] clinical trial comparing the [[effectiveness]] and [[safety]] of PSA-DBS vs. VIM-DBS, 11 patients with refractory ET will undergo a multi-domain neuropsychological battery assessment. This will include a pre-/post-implantation assessment (3 months after the stimulation of each target and 6 months after an open stage of DBS on the most optimal target).

Evidence on the neuropsychological effects of DBS in patients with refractory ET is very scarce, particularly in lesser-explored targets such as PSA. This study could contribute significantly in this field, particularly on pre-procedure safety analysis for tailored patient/technique selection, and to complete the safety analysis of the procedure. Moreover, if proven useful, this proposed neuropsychological assessment protocol could be extensible to other surgical therapies for ET
((Triguero-Cueva L, Marín-Romero B, Madrid-Navarro CJ, Pérez-Navarro MJ, Iáñez-Velasco B, Mínguez-Castellanos A, Katati MJ, Escamilla-Sevilla F. Neuropsychological assessment protocol in an ongoing randomized controlled trial on posterior [[subthalamic area]] vs. ventral intermediate nucleus deep brain stimulation for essential tremor. Front Neurol. 2023 Oct 30;14:1222592. doi: 10.3389/fneur.2023.1222592. PMID: 38020655; PMCID: PMC10643533.))
===== Case series =====
Twenty patients with ET with DBS had standardized video-documented examinations at baseline, in the stimulation-on condition at short term (13.1 ± 1.9 months since surgery, mean ± SEM), and in the stimulator switched on and off (stim-ON/OFF) at long term; all assessments were done between 32 and 120 months (71.9 ± 6.9 months) after implantation. The primary outcome was the Tremor Rating Scale (TRS) blindly assessed by 2 trained movement disorder neurologists. Secondary outcomes were TRS subscores A, B, and C; Archimedes spiral score; and activities of daily living score. At long-term follow-up, tremor was additionally recorded with accelerometry. The rebound effect after switching the stimulator off was assessed for 1 hour in a subgroup.

Results: Tremor severity worsened considerably over time in both in the nonstimulated and stimulated conditions. Vim-DBS improved the TRS in the short term and long term significantly. The spiral score and functional measures showed similar improvements. All changes were highly significant. However, the stimulation effect was negatively correlated with time since surgery (ρ = -0.78, p < 0.001). This was also true for the secondary outcomes. Only one-third of the patients had a rebound effect terminated 60 minutes after the stimulator was switched off. Long-term worsening of the TRS was more profound during stim-ON than in the stim-OFF condition, indicating habituation to stimulation.

Conclusion: Vim-DBS loses efficacy over the long term. Efforts are needed to improve the long-term efficacy of Vim-DBS
((Paschen S, Forstenpointner J, Becktepe J, Heinzel S, Hellriegel H, Witt K, Helmers AK, Deuschl G. Long-term efficacy of deep brain stimulation for essential tremor: An observer-blinded study. Neurology. 2019 Mar 19;92(12):e1378-e1386. doi: 10.1212/WNL.0000000000007134. Epub 2019 Feb 20. PMID: 30787161.)).

===== References =====