Probabilistic mapping of the antidystonic effect of pallidal neurostimulation: a multicentre imaging study

Reich, Martin M.; Horn, Andreas; Lange, Florian; Roothans, Jonas; Paschen, Steffen; Runge, Joachim; Wodarg, Fritz; Pozzi, Nicoló Gabriele; Witt, Karsten; Nickl, Robert; Soussand, Louis; Ewert, Siobhan; Maltese, Virgina; Wittstock, Matthias; Schneider, Gerd‐Helge; Coenen, Volker A.; Mahlknecht, Philipp; Poewe, Werner; Eisner, Wilhelm; Helmers, Ann‐Kristin; Matthies, Cordula; Sturm, Volker; Isaias, Ioannis U.; Krauss, Joachim K.; Kühn, Andrea A.; Deuschl, Günther; Volkmann, Jens

doi:10.1093/brain/awz046

Cited by 114 publications

(172 citation statements)

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“…The largest coverage of VTAs was observed for the subpallidal area below the lateral GPi and medial GPe. This is in line with recently published results where the optimal antidystonic spot also covered the subpallidal area [15]. It is likely that the stimulation of efferent pallidothalamic fibres brings about most of the therapeutic effects observed in dystonia patients [21][22][23].…”

Section: Discussionsupporting

confidence: 91%

“…Another study correlating theta oscillations with clinical outcome in CD patients localized the optimal spot for stimulation within the posterior third of the GPi [19]. A recent multicenter study in patients with cervical and generalized dystonia applied a probabilistic approach and suggested that the optimal spot for antidystonic effects was the ventro-posterior GPi and the adjacent subpallidal white matter [15]. In our study, the average commissure-based lead location is slightly distant from the target reported by Reich et al with a more lateral electrode localization in the present study (x = 21.4 ± 1.5 mm vs. Reich et al 19.8 ± 1.8 mm) [15].…”

Section: Discussionmentioning

confidence: 99%

“…A recent multicenter study in patients with cervical and generalized dystonia applied a probabilistic approach and suggested that the optimal spot for antidystonic effects was the ventro-posterior GPi and the adjacent subpallidal white matter [15]. In our study, the average commissure-based lead location is slightly distant from the target reported by Reich et al with a more lateral electrode localization in the present study (x = 21.4 ± 1.5 mm vs. Reich et al 19.8 ± 1.8 mm) [15]. Programming in all of our dystonia patients was not limited by pyramidal side effects and none of our patients experienced speech or gait disturbances during long-term stimulation [20].…”

Section: Discussionmentioning

confidence: 99%

“…According to a previous study motor symptoms were assessed with the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) in CD patients and with the Burke Fahn Marsden Dystonia Rating Scale (BFMDRS) in GD patients [15]. Non-blinded motor ratings were based on standardized video recordings.…”

Section: Methodsmentioning

confidence: 99%

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Pallidal lead placement in dystonia: leads of non-responders are contained within an anatomical range defined by responders

et al. 2020

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Background Deep brain stimulation (DBS) within the pallidum represents an effective and well-established treatment for isolated dystonia. However, clinical outcome after surgery may be variable with limited response in 10-25% of patients. The effect of lead location on clinical improvement is still under debate. Objective To identify stimulated brain regions associated with the most beneficial clinical outcome in dystonia patients. Methods 18 patients with cervical and generalized dystonia with chronic DBS of the internal pallidum were investigated. Patients were grouped according to their clinical improvement into responders, intermediate responders and non-responders. Magnetic resonance and computed tomography images were co-registered, and the volume of tissue activated (VTA) with respect to the pallidum of individual patients was analysed. Results VTAs in responders (n = 11), intermediate responders (n = 3) and non-responders (n = 4) intersected with the posterior internal (GPi) and external (GPe) pallidum and the subpallidal area. VTA heat maps showed an almost complete overlap of VTAs of responders, intermediate and non-responders. VTA coverage of the GPi was not higher in responders. In contrast, VTAs of intermediate and non-responders covered the GPi to a significantly larger extent in the left hemisphere (p < 0.01).Conclusions DBS of ventral parts of the posterior GPi, GPe and the adjacent subpallidal area containing pallidothalamic output projections resulted in favourable clinical effects. Of note, non-responders were also stimulated within the same area. This suggests that factors other than mere lead location (e.g., clinical phenotype, genetic background) have determined clinical outcome in the present cohort.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Pallidal lead placement in dystonia: leads of non-responders are contained within an anatomical range defined by responders

et al. 2020

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“…However, the theoretical concept of VTA modelling constitutes a simplification that neglects factors like fiber orientation (Anderson et al, 2019). Regarding the concept of predicting effects of deep brain stimulation in relation to the anatomical target area there have been several approaches in the past, such as investigating lead positions (Delcour et al, 2011;Camalier et al, 2014;Barbe et al, 2018;Dafsari et al, 2018), the creation of probabilistic sweet spots (Eisenstein et al, 2014;Dembek et al, 2017;Dembek et al, 2019b;Reich et al, 2019), and the estimation of beneficial Running head: Networks in DBS-induced dysarthria connectivity profiles (Horn et al, 2017;Al-Fatly et al, 2019). In this study, we focused on providing an atlas structure that is easy to implement in planning and programming software and therefore decided to base our predictive model on an approach introduced by Baldermann et al (Baldermann et al, 2019).…”

Section: Methodological Considerations and Limitationsmentioning

confidence: 99%

Network fingerprint of stimulation-induced speech impairment in essential tremor

Petry‐Schmelzer

Jergas

Thies

et al. 2020

Preprint

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Word count abstract: 384/400Word count introduction: 440 Word count discussion: 1769Word count text: 4769/6000 Abstract Thalamic deep brain stimulation (DBS) is an effective treatment for patients with medically refractory essential tremor. However, stimulation-induced side-effects, especially stimulationinduced dysarthria (SID), interfere severely with quality of life and postoperative tremor control. Here, we present a functional and structural network approach to SID to gain insights into the associated brain areas and to predict stimulation-induced worsening of intelligibility. Monopolar reviews were conducted in 14 essential tremor patients with bilateral thalamic DBS by increasing the stimulation amplitude contact-wise until (i) a maximum of 10mA, (ii) the occurrence of intolerable side effects, or (iii) the onset of SID. Speech assessments included intelligibility ratings when reading a German standard text and a fast syllable repetition task.To detect brain areas associated with SID, a functional connectivity difference image of volumes of tissue activated (VTAs) causing SID, and VTAs not causing SID was created employing a state-of-the-art functional connectome, Lead-DBS, as well as the SPM toolbox.Additionally, discriminative fibers for stimulation-induced worsening of intelligibility were identified in a structural connectome using linear mixed effect models and validated in a leaveone-out design. A total of 111 contact assessments were included for further analysis. The functional connectivity difference image indicated stronger connectivity of VTAs causing SID (N = 51) to the precentral gyrus with a positive medio-lateral gradient, parts of the inferior and medial frontal gyrus, the supramarginal gyrus, the superior temporal gyrus, as well as the superior and the inferior cerebellar lobules, and the vermis. In the thalamic region, discriminative fibers for stimulation-induced worsening of intelligibility were located anterolaterally to fibers associated with tremor control as published by Al-Fatly et al. (2019). The overlap of the respective clinical stimulation setting's VTAs with these fibers explained 33.2% of the variance of individual change in intelligibility compared to "OFF stimulation" in a leaveone-out design. This study demonstrates that SID in essential tremor patients is related to a modulation of the functional connectome of speech production by thalamic DBS. In spite of the Running head: Networks in DBS-induced dysarthria proximity of functional and structural connectivity patterns for tremor control, as identified by Al-Fatly et al. (2019), and deterioration of speech, as identified in the present study, we were able to derive a fiber-based atlas structure, that could help to avoid SID in essential tremor patients. These findings might contribute to future lead placement and postoperative programming strategies.Keywords: thalamic deep brain stimulation, speech motor system, intelligibility, dysarthria, volume of tissue activated Abbreviations DBS = deep brain stimulation, DDK = diadoc...

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Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease

Dembek

Roediger

Horn

et al. 2019

Annals of Neurology

139

203

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ObjectiveTo investigate whether functional sweet spots of deep brain stimulation (DBS) in the subthalamic nucleus (STN) can predict motor improvement in Parkinson disease (PD) patients.MethodsStimulation effects of 449 DBS settings in 21 PD patients were clinically and quantitatively assessed through standardized monopolar reviews and mapped into standard space. A sweet spot for best motor outcome was determined using voxelwise and nonparametric permutation statistics. Two independent cohorts were used to investigate whether stimulation overlap with the sweet spot could predict acute motor outcome (10 patients, 163 settings) and long‐term overall Unified Parkinson's Disease Rating Scale Part III (UPDRS‐III) improvement (63 patients).ResultsSignificant clusters for suppression of rigidity and akinesia, as well as for overall motor improvement, resided around the dorsolateral border of the STN. Overlap of the volume of tissue activated with the sweet spot for overall motor improvement explained R2 = 37% of the variance in acute motor improvement, more than triple what was explained by overlap with the STN (R2 = 9%) and its sensorimotor subpart (R2 = 10%). In the second independent cohort, sweet spot overlap explained R2 = 20% of the variance in long‐term UPDRS‐III improvement, which was equivalent to the variance explained by overlap with the STN (R2 = 21%) and sensorimotor STN (R2 = 19%).InterpretationThis study is the first to predict clinical improvement of parkinsonian motor symptoms across cohorts based on local DBS effects only. The new approach revealed a distinct sweet spot for STN DBS in PD. Stimulation overlap with the sweet spot can predict short‐ and long‐term motor outcome and may be used to guide DBS programming. ANN NEUROL 2019;86:527–538

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Probabilistic mapping of the antidystonic effect of pallidal neurostimulation: a multicentre imaging study

Cited by 114 publications

References 38 publications

Pallidal lead placement in dystonia: leads of non-responders are contained within an anatomical range defined by responders

Pallidal lead placement in dystonia: leads of non-responders are contained within an anatomical range defined by responders

Network fingerprint of stimulation-induced speech impairment in essential tremor

Probabilistic sweet spots predict motor outcome for deep brain stimulation in Parkinson disease

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