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Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

ABSTRACT: The aim of this study was to assess the effects of novel stimulation algorithms of deep brain stimulation (short pulse and directional stimulation) in the ventrointermediate thalamus and posterior subthalamic area (VIM/PSA-DBS) on tremor in Parkinson's disease (PD) and to compare the effects with those in essential tremor (ET). We recruited six PD patients (70.8 ± 10.4 years) and seven ET patients (64.4 ± 9.9 years) with implanted VIM/PSA-DBS in a stable treatment condition (> 3 months postoperatively). Tremor severity and ataxia were assessed in four different stimulation conditions in a randomized order: DBS switched off (STIM OFF), omnidirectional stimulation with 60 µs (oDBS60), omnidirectional stimulation with 30 µs (oDBS30), directional stimulation at the best segment with 60 µs (dDBS60). In both patient groups, all three DBS stimulation modes reduced the total tremor score compared to STIM OFF, whereas stimulation-induced ataxia was reduced by oDBS30 and partially by dDBS60 compared to oDBS60. Tremor reduction was more pronounced in PD than in ET due to a limited DBS effect on intention and action-specific drawing tremor in ET. In PD and ET tremor, short pulse or directional VIM/PSA-DBS is an effective and well tolerated therapeutic option.Trial registration: The study was registered in the DRKS (ID DRKS00025329, 18.05.2021, German Clinical Trials Register, DRKS-Deutsches Register Klinischer Studien).

SUBMITTER: Hidding U

PROVIDER: S-EPMC9068767 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

Hidding Ute U Schaper Miriam M Gulberti Alessandro A Buhmann Carsten C Gerloff Christian C Moll Christian K E CKE Hamel Wolfgang W Choe Chi-Un CU Pötter-Nerger Monika M

Scientific reports 20220504 1

The aim of this study was to assess the effects of novel stimulation algorithms of deep brain stimulation (short pulse and directional stimulation) in the ventrointermediate thalamus and posterior subthalamic area (VIM/PSA-DBS) on tremor in Parkinson's disease (PD) and to compare the effects with those in essential tremor (ET). We recruited six PD patients (70.8 ± 10.4 years) and seven ET patients (64.4 ± 9.9 years) with implanted VIM/PSA-DBS in a stable treatment condition (> 3 months postopera ...[more]

PMID: 35508680

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Project description:ObjectiveObservational studies utilising diffusion tractography have suggested a common mechanism for tremor alleviation in deep brain stimulation for essential tremor: the decussating portion of the dentato-rubro-thalamic tract. We hypothesised that directional stimulation of the dentato-rubro-thalamic tract would result in greater tremor improvement compared to sham programming, as well as comparable improvement as more tedious standard-of-care programming.MethodsA prospective, blinded crossover trial was performed to assess the feasibility, safety and outcomes of programming based solely on dentato-rubro-thalamic tract anatomy. Using magnetic resonance imaging diffusion-tractography, the dentato-rubro-thalamic tract was identified and a connectivity-based treatment setting was derived by modelling a volume of tissue activated using directional current steering oriented towards the dentato-rubro-thalamic tract centre. A sham setting was created at approximately 180° opposite the connectivity-based treatment. Standard-of-care programming at 3 months was compared to connectivity-based treatment and sham settings that were blinded to the programmer. The primary outcome measure was percentage improvement in the Fahn-Tolosa-Marín tremor rating score compared to the preoperative baseline.ResultsAmong the six patients, tremor rating scores differed significantly among the three experimental conditions (P=0.030). The mean tremor rating score improvement was greater with the connectivity-based treatment settings (64.6% ± 14.3%) than with sham (44.8% ± 18.6%; P=0.031) and standard-of-care programming (50.7% ± 19.2%; P=0.062). The distance between the centre of the dentato-rubro-thalamic tract and the volume of tissue activated inversely correlated with the percentage improvement in the tremor rating score (R2=0.24; P=0.04). No significant adverse events were encountered.ConclusionsUsing a blinded, crossover trial design, we have shown the technical feasibility, safety and potential efficacy of connectivity-based stimulation settings in deep brain stimulation for treatment of essential tremor.

Project description:The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Project description:Deep Brain Stimulation of the posterior subthalamic area is an emergent target for the treatment of Essential Tremor. Due to the heterogeneous and complex anatomy of the posterior subthalamic area, it remains unclear which specific structures mediate tremor suppression and different side effects. The objective of the current work was to yield a better understanding of what anatomical structures mediate the different clinical effects observed during directional deep brain stimulation of that area. We analysed a consecutive series of 12 essential tremor patients. Imaging analysis and systematic clinical testing performed 4-6 months postoperatively yielded location, clinical efficacy and corresponding therapeutic windows for 160 directional contacts. Overlap ratios between individual activation volumes and neighbouring thalamic and subthalamic nuclei as well as individual fiber tracts were calculated. Further, we generated stimulation heatmaps to assess the area of activity and structures stimulated during tremor suppression and occurrence of side effects. Stimulation of the dentato-rubro-thalamic tract and the zona incerta was most consistently correlated with tremor suppression. Both individual and group analysis demonstrated a similar pattern of activation for tremor suppression and different sorts of side-effects. Unlike current clinical concepts, induction of spasms and paresthesia were not correlated with stimulation of the corticospinal tract and the medial lemniscus. Furthermore, we noticed a significant difference in the therapeutic window between the best and worst directional contacts. The best directional contacts did not provide significantly larger therapeutic windows than omnidirectional stimulation at the same level. Deep brain stimulation of the posterior subthalamic area effectively suppresses all aspects of ET but can be associated with concomitant side effects limiting the therapeutic window. Activation patterns for tremor suppression and side effects were similar and predominantly involved the dentato-rubro-thalamic tract and the zona incerta. We found no different activation patterns between different types of side effects and no clear correlation between structure and function. Future studies with use of more sophisticated modelling of activation volumes taking into account fiber heterogeneity and orientation may eventually better delineate these different clusters, which may allow for a refined targeting and programming within this area.

Dataset Information

Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

Publications

Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

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