The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE)

Kai, Li; Coenen, Volker A.; Gonçalves-Ferreira, António; Boon, Paul; Elger, Christian E.; Taylor, Rod S; Ryvlin, Philippe; Gil‐Nagel, Antonio; Gielen, F.L.H.; Brionne, Thomas C.; Abouihia, Abdallah; Beth, Grégory

doi:10.1093/neuros/nyy023

Cited by 66 publications

(64 citation statements)

References 16 publications

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“…This electrode was implanted using an extraventricular approach and was placed posterolaterally to the target at the border between the ventral lateral nucleus and the ANT instead of in the ANT proper. In a study of patients who underwent ANT DBS for refractory epilepsy, Lehtimäki et al found that 29.5% of the extraventricular approach DBS placements and 10.3% of the transventricular approach DBS placements were off target. This highlights a relatively common complication of ANT placement of which providers should be aware and illustrates that postoperative imaging is essential in confirming accurate surgical placement.…”

Section: Discussionmentioning

confidence: 99%

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment‐resistant multifocal epilepsy

Elder¹,

Friedman²,

Devinsky³

et al. 2019

Epilepsia Open

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Summary Electrical stimulation in the anterior nucleus of the thalamus (ANT) has previously been found to be efficacious for reducing seizure frequency in patients with epilepsy. Bilateral deep brain stimulation (DBS) of the ANT is an open‐loop system that can be used in the management of treatment‐resistant epilepsy. In contrast, the responsive neurostimulation (RNS) system is a closed‐loop device that delivers treatment in response to prespecified electrocorticographic triggers. The efficacy and safety of RNS targeting the ANT is unknown. We describe 3 patients with treatment‐resistant multifocal epilepsy who were implanted with an RNS system, which included unilateral stimulation of the ANT. After >33 months of follow‐up, there were no adverse effects on mood, memory or behavior. Two patients had ≥50% reduction in disabling seizures and one patient had a 50% reduction compared to pretreatment baseline. Although reduction in seizure frequency has been modest to date, these findings support responsive neurostimulation of the ANT as feasible, safe, and well‐tolerated. Further studies are needed to determine optimal stimulation parameters.

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Section: Discussionmentioning

confidence: 99%

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment‐resistant multifocal epilepsy

Elder¹,

Friedman²,

Devinsky³

et al. 2019

Epilepsia Open

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“…18,44 One potential cause for outcome variation is inadequate DBS targeting: for instance, approximately 10% of electrodes were not within the ANT in the SANTE trial and the Medtronic Registry for Epilepsy (MORE) study. 30,50 Suggested improvements in direct ANT targeting have been proposed; 10,40 however, insufficiencies in direct structural targeting in DBS have been previously illustrated. 36,37 In this pilot study, we aimed to assess potential differences in resting-state functional connectivity profiles from volumes of tissue activated (VTAs) after ANT DBS in responders and nonresponders.…”

mentioning

confidence: 99%

Differences in functional connectivity profiles as a predictor of response to anterior thalamic nucleus deep brain stimulation for epilepsy: a hypothesis for the mechanism of action and a potential biomarker for outcomes

Middlebrooks

Grewal

Stead³

et al. 2018

Neurosurgical Focus

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OBJECTIVEDeep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a promising therapy for refractory epilepsy. Unfortunately, the variability in outcomes from ANT DBS is not fully understood. In this pilot study, the authors assess potential differences in functional connectivity related to the volume of tissue activated (VTA) in ANT DBS responders and nonresponders as a means for better understanding the mechanism of action and potentially improving DBS targeting.METHODSThis retrospective analysis consisted of 6 patients who underwent ANT DBS for refractory epilepsy. Patients were classified as responders (n = 3) if their seizure frequency decreased by at least 50%. The DBS electrodes were localized postoperatively and VTAs were computationally generated based on DBS programming settings. VTAs were used as seed points for resting-state functional MRI connectivity analysis performed using a control dataset. Differences in cortical connectivity to the VTA were assessed between the responder and nonresponder groups.RESULTSThe ANT DBS responders showed greater positive connectivity with the default mode network compared to nonresponders, including the posterior cingulate cortex, medial prefrontal cortex, inferior parietal lobule, and precuneus. Interestingly, there was also a consistent anticorrelation with the hippocampus seen in responders that was not present in nonresponders.CONCLUSIONSBased on their pilot study, the authors observed that successful ANT DBS in patients with epilepsy produces increased connectivity in the default mode network, which the authors hypothesize increases the threshold for seizure propagation. Additionally, an inhibitory effect on the hippocampus mediated through increased hippocampal γ-aminobutyric acid (GABA) concentration may contribute to seizure suppression. Future studies are planned to confirm these findings.

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“…The Oslo study used an extraventricular approach, which may make it even more difficult to hit the central part of ANT. A consensus report based on an international multicenter registry have recently concluded that direct targeting and a transventricular approach should be preferred for DBS implantations to the ANT . The success rate when placing at least one contact at the ANT target region bilaterally was 84% with a transventricular route, compared to 58% with an extraventricular route …”

Section: Discussionmentioning

confidence: 99%

“…Later studies have discussed the importance of a correct implantation site and advocated that direct MRI visualization of the desired target is essential for a favorable outcome in ANT‐DBS . ANT target identification in the Oslo patients was performed in the same way as in the SANTE study, using the same coordinates that were described in the pilot studies listed in the original SANTE article, and that were confirmed through personal communication with the SANTE authors.…”

Section: Introductionmentioning

confidence: 97%

Direct visual targeting versus preset coordinates for ANT‐DBS in epilepsy

Nome

Herrman

Kai³

et al. 2020

Acta Neurol Scand

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Deep brain stimulation (DBS) of the anterior nucleus of thalamus (ANT) is an evolving treatment option in refractory focal epilepsy. 1,2 The SANTE study 3 was for a long time the only randomized double-blinded trial with bilateral implantation of DBS electrodes to the ANT. They found that bilateral ANT stimulation reduced seizures with a sustained effect for 2 years. An open follow-up continuation of the study showed reduction in the median seizure frequency by 69% from baseline after 5 years of stimulation. 4 Funding informationThis project has been made possible by Dam Foundation.Objectives: Deep brain stimulation (DBS) of the anterior thalamic nucleus (ANT) may be used against refractory focal epilepsy, but only two randomized double-blinded trials have been performed. The Oslo study was discontinued prematurely since reduction in seizure frequency was less than expected. The aim of the present study was to review the targeting used in the Oslo study and to identify the actual positions of the contacts used for stimulation. Material and methods:BrainLab MRI data were available from 12 Oslo study patients. Based on MRI the coordinates of the center of the ANT were identified. The coordinates were considered as the visually identified preferred target and were compared with the target originally used for ANT electrode implantation and with the actual electrode positions estimated from post-operative CT scans. Results:We found considerable differences between the visually identified preferred target, the originally planned target, and the actual electrode position. The total distance between the active electrode position and the visually identified preferred target was on average 3.3 mm on the right and 2.9 mm on the left side. Conclusion:Indirect targeting based on preset coordinates may contribute to explain the modest effect of ANT-DBS on seizure frequency seen in the Oslo study.Observed differences between the center of the ANT and the actual electrode position may at least in part be explained by variations in position and size of the ANT. Direct identification of the target using better MRI imaging protocols is recommended for future ANT-DBS surgery. K E Y W O R D Santerior nucleus of thalamus, deep brain stimulation, epilepsy 24 | NOME Et al.

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The Surgical Approach to the Anterior Nucleus of Thalamus in Patients With Refractory Epilepsy: Experience from the International Multicenter Registry (MORE)

Cited by 66 publications

References 16 publications

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment‐resistant multifocal epilepsy

Responsive neurostimulation targeting the anterior nucleus of the thalamus in 3 patients with treatment‐resistant multifocal epilepsy

Differences in functional connectivity profiles as a predictor of response to anterior thalamic nucleus deep brain stimulation for epilepsy: a hypothesis for the mechanism of action and a potential biomarker for outcomes

Direct visual targeting versus preset coordinates for ANT‐DBS in epilepsy

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