Neurophysiologic Characteristics of the Anterior Nucleus of the Thalamus during Deep Brain Stimulation Surgery for Epilepsy.

INTRODUCTION: Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an increasingly promising treatment option for refractory epilepsy. Optimal therapeutic benefit has been associated with stimulation at the junction of ANT and the mammillothalamic tract (mtt), but electrophysiologic markers of this target are lacking. The present study examined microelectrode recordings (MER) during DBS to identify unique electrophysiologic characteristics of ANT and the ANT-mtt junction. METHODS: Ten patients with medically refractory epilepsy underwent MER during ANT-DBS implantation under general anesthesia. MER locations were determined based on coregistration of preoperative MRI, postoperative CT, and a stereotactic atlas of the thalamus (Morel atlas). Several neurophysiological parameters including single unit spiking rate, bursting properties, theta and alpha power and cerebrospinal fluid (CSF)-normalized root mean square (NRMS) of multiunit activity were characterized at recording depths and compared to anatomic boundaries. RESULTS: From sixteen hemispheres, 485 recordings locations were collected from a mean of 30.3 (15.64 ± 5.0 mm) recording spans. Three-hundred and ninety-four of these recording locations were utilized further for analysis of spiking and bursting rates, after excluding recordings that were more than 8 mm above the putative ventral ANT border. The ANT region exhibited discernible features including: (1) mean spiking rate (7.52 Hz ± 6.9 Hz; one-way analysis of variance test, p = 0.014 when compared to mediodorsal nucleus of the thalamus [MD], mtt, and CSF), (2) the presence of bursting activity with 40% of ANT locations (N = 59) exhibited bursting versus 24% the mtt (χ2; p < 0.001), and 32% in the MD (p = 0.38), (3) CSF-NRMS, a proxy for neuronal density, exhibited well demarcated changes near the entry and exit of ANT (linear regression, R = -0.33, p < 0.001). Finally, in the ANT, both theta (4-8 Hz) and alpha band power (9-12 Hz) were negatively correlated with distance to the ventral ANT border (linear regression, p < 0.001 for both). The proportion of recordings with spiking and bursting activity was consistently highest 0-2 mm above the ventral ANT border with the mtt. CONCLUSION: We observed several electrophysiological markers demarcating the ANT superior and inferior borders including multiple single cell and local field potential features. A local maximum in neural activity just above the ANT-mtt junction was consistent with the previously described optimal target for seizure reduction. These features may be useful for successful targeting of ANT-DBS for epilepsy.

Deep brain stimulation of anterior nucleus and centromedian nucleus of thalamus in treatment for drug-resistant epilepsy.

INTRODUCTION: Drug-resistant epilepsy (DRE) remains poorly-controlled in c.33% of patients, and up to 50% of patients suffering from DRE are deemed not to be suitable candidates for resective surgery. For these patients, deep brain stimulation (DBS) may constitute the last resort in the treatment of DRE. STATE OF THE ART: We undertook a systematic review of the current literature on DBS efficacy and the safety of two thalamic nuclei-anterior nucleus of the thalamus (ANT) and the centromedian nucleus of the thalamus in the management of patients with DRE. A search using two electronic databases, the Medical Literature, Analysis, and Retrieval System on-line (MEDLINE) and the Cochrane Central Register of Controlled Trials (CEN-TRAL) was conducted. CLINICAL IMPLICATIONS: We found 30 articles related to ANT DBS and 13 articles related to CMN DBS which were further analysed. Based on the clinical research articles, we found a mean seizure frequency reduction for both thalamic nuclei. For ANT DBS, the mean seizure frequency reduction ranged from 48% to 75%, and for CMN DBS from 46.7% to 91%. The responder rate (defined as at least 50% reduction in seizure frequency) was reported to be 53.2-75% for patients after ANT DBS and 50-90% for patients after CMN DBS. FUTURE DIRECTIONS: ANT and CMN DBS appear to be safe and efficacious treatments, particularly in patients with refractory partial seizures and primary generalised seizures. ANT DBS reduces most effectively seizures originating in the temporal and frontal lobes. CMN DBS reduces mostly primary generalised tonic-clonic and atypical absences and atonic seizures. Seizures related to Lennox-Gastaut syndrome respond very favourably to CMN DBS.

Multitarget deep brain stimulation for epilepsy.

OBJECTIVE: Deep brain stimulation (DBS) is a rapidly growing surgical option for patients with drug-resistant epilepsy who are not candidates for resective/ablative surgery. Recent randomized controlled trials have demonstrated efficacy of DBS of the anterior nucleus of the thalamus (ANT), particularly in frontal or temporal epilepsy, whereas DBS of the centromedian (CM) nucleus appears to be most suitable in well-defined generalized epilepsy syndromes. At the authors' institution, DBS candidates who did not fit the populations represented in these trials were managed with DBS of multiple distinct targets, which included ANT, CM, and less-studied nuclei-i.e., mediodorsal nucleus, pulvinar, and subthalamic nucleus. The goal of this study was to present the authors' experience with these types of cases, and to motivate future investigations that can determine the long-term efficacy of multitarget DBS. METHODS: This single-center retrospective study of adult patients with drug-resistant epilepsy who underwent multitarget DBS was performed to demonstrate the feasibility and safety of this approach, and to present seizure outcomes. Patients in this cohort had epilepsy with features that were difficult to treat with DBS of the ANT or CM nucleus alone, including multifocal/multilobar, diffuse-onset, and/or posterior-onset seizures; or both generalized and focal seizures. RESULTS: Eight patients underwent DBS of 2-3 distinct thalamic/subthalamic nuclei. DBS was performed with 2 electrodes in each hemisphere. All leads in each patient were implanted with either frontal or parietal trajectories. There were no surgical complications. Among those with > 6 months of follow-up (n = 5; range 7-21 months), all patients were responders in terms of overall seizure frequency and/or convulsive seizure frequency (i.e., ≥ 50% reduction). Two patients had adverse stimulation effects, which resolved with further programming. CONCLUSIONS: Multitarget DBS is a procedurally feasible and safe treatment strategy to maximize outcomes in patients with complex epilepsy. The authors highlight their approach to inform future studies that are sufficiently powered to assess its efficacy.

Multifocal drug-resistant epilepsy in a patient with a newly discovered mutation in tuberous sclerosis complex 1 gene treated by deep brain stimulation in the anterior thalamic nucleus.

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the tumor suppressor genes TSC1 or TSC2. TSC is characterized by the formation of multiple tumors in various organs. The most common neurological manifestation of the disorder is epilepsy present in 79-90% of cases. At least one-third of TSC patients develop drug-resistant epilepsy (DRE) which remains a great challenge for clinicians. Neuromodulation is an option in cases of multifocal epilepsy, epilepsy originating in eloquent areas, or the inability to identify the ictal onset zone. Deep brain stimulation of the anterior thalamic nucleus (ANT-DBS) may be used in the treatment of multifocal DRE. Here, we present a case of a patient with multifocal DRE caused by TSC, who was treated with ANT-DBS. A follow-up period of eight months showed that the patient's multifocal DRE was successfully treated by ANT-DBS.

Sensing with deep brain stimulation device in epilepsy: Aperiodic changes in thalamic local field potential during seizures.

OBJECTIVE: Thalamic deep brain stimulation (DBS) is an effective therapeutic option in patients with drug-resistant epilepsy. Recent DBS devices with sensing capabilities enable chronic, outpatient local field potential (LFP) recordings. Whereas beta oscillations have been demonstrated to be a useful biomarker in movement disorders, the clinical utility of DBS sensing in epilepsy remains unclear. Our aim was to determine LFP features that distinguish ictal from inter-ictal states, which may aid in tracking seizure outcomes with DBS. METHODS: Electrophysiology data were obtained from DBS devices implanted in the anterior nucleus (N = 12) or centromedian nucleus (N = 2) of the thalamus. Power spectra recorded during patient/caregiver-marked seizure events were analyzed with a method that quantitatively separates the oscillatory and non-oscillatory/aperiodic components of the LFP using non-parametric statistics, without the need for pre-specification of the frequency bands of interest. Features of the LFP parameterized using this algorithm were compared with those from inter-ictal power spectra recorded in clinic. RESULTS: Oscillatory activity in multiple canonical frequency bands was identified from the power spectra in 86.48% of patient-marked seizure events. Delta oscillations were present in all patients, followed by theta (N = 10) and beta (N = 9). Although there were no differences in oscillatory LFP features between the ictal and inter-ictal states, there was a steeper decline in the 1/f slope of the aperiodic component of the LFP during seizures. SIGNIFICANCE: Our work highlights the potential and shortcomings of chronic LFP recordings in thalamic DBS for epilepsy. Findings suggest that no single frequency band in isolation clearly differentiates seizures, and that features of aperiodic LFP activity may be clinically-relevant biomarkers of seizures.

Functional connectomic profile correlates with effective anterior thalamic stimulation for refractory epilepsy.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. OBJECTIVES: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. METHODS: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. RESULTS: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p < 0.001 vs ANT-atlas: |r| = 0.715, p = 0.001), which remained significant when controlling for the extent of the seizure foci (|r| = 0.773, p < 0.001) and the distance between the seizure foci and DBS site (|r| = 0.777, p < 0.001). Significant correlations were independent of variance in the DBS sites (|r| = 0.148, p = 0.57). CONCLUSION: These findings suggest that functional connectomic profile is a potential reliable non-invasive biomarker to predict ANT-DBS outcomes. Accordingly, the identification of ANT responders could decrease the surgical risk for patients who may not benefit and optimize the cost-effective allocation of health care resources.

Clinical efficacy and safety of anterior thalamic deep brain stimulation for intractable drug resistant epilepsy.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) is a neuromodulation therapy for patients with refractory focal seizures evolving into bilateral tonic-clonic seizures when pharmacotherapy as well other neuromodulation techniques including vagus nerve stimulation or responsive neurostimulation have failed. OBJECTIVE: We performed a prospective single-center study investigating the clinical efficacy and exact ANT DBS lead location in patients with DRE. METHODS: The primary outcome measure was the proportion of patients with more than 50 % reduction in diary-recorded seizures when compared to three preoperative months (baseline seizure frequency). The close postoperative follow-up was performed every 3 months. The seizure frequency, stimulation settings and adverse events were closely monitored during follow-up visits. We also analyzed the seizure outcome with location of ANT DBS active contacts. RESULTS: Between May 2020 and October 2022, 10 adult patients with a mean age of 38.5 years (range, 30-48 years) underwent bilateral ANT DBS surgery (mean duration of DRE 28.6 years, range 16-41 years). The median seizure count in three months period preceding surgery (baseline seizure count) was 43.2 (range, 4-150). Nine patients achieved more than 50 % seizure reduction at the last follow-up (mean range 3-33 13.6 months, months). ANT DBS caused seizure reduction 3 months after procedure as well as at last follow-up by 60.4 % and 73.3 %, respectively. Due to relatively small number of studying individuals we cannot precisely locate the area within ANT associated with good clinical outcome. Patients with temporal lobe epilepsy had a remarkable reduction of seizure frequency. No patient suffered transient or permanent neurological deficits. CONCLUSIONS: Clinical efficacy of ANT DBS may support more widespread utilization of this neuromodulation technique especially for seizures originating from temporal lobes.

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity.

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

Functional network dynamics between the anterior thalamus and the cortex in deep brain stimulation for epilepsy.

Owing to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the anterior nucleus of the thalamus (ANT) has been proposed as a key deep brain stimulation (DBS) target in drug-resistant epilepsy. However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 patients with drug-resistant epilepsy (n = 6 males, age = 41.6 ± 13.79 years) underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude θ (4-8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the θ band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20-70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG θ oscillations, higher θ power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of θ oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with drug-resistant epilepsy.

Deep brain stimulation for patients with refractory epilepsy: nuclei selection and surgical outcome.

Objective: By studying the surgical outcome of deep brain stimulation (DBS) of different target nuclei for patients with refractory epilepsy, we aimed to explore a clinically feasible target nucleus selection strategy. Methods: We selected patients with refractory epilepsy who were not eligible for resective surgery. For each patient, we performed DBS on a thalamic nucleus [anterior nucleus of the thalamus (ANT), subthalamic nucleus (STN), centromedian nucleus (CMN), or pulvinar nucleus (PN)] selected based on the location of the patient's epileptogenic zone (EZ) and the possible epileptic network involved. We monitored the clinical outcomes for at least 12 months and analyzed the clinical characteristics and seizure frequency changes to assess the postoperative efficacy of DBS on the different target nuclei. Results: Out of the 65 included patients, 46 (70.8%) responded to DBS. Among the 65 patients, 45 underwent ANT-DBS, 29 (64.4%) responded to the treatment, and four (8.9%) of them reported being seizure-free for at least 1 year. Among the patients with temporal lobe epilepsy (TLE, n = 36) and extratemporal lobe epilepsy (ETLE, n = 9), 22 (61.1%) and 7 (77.8%) responded to the treatment, respectively. Among the 45 patients who underwent ANT-DBS, 28 (62%) had focal to bilateral tonic-clonic seizures (FBTCS). Of these 28 patients, 18 (64%) responded to the treatment. Out of the 65 included patients, 16 had EZ related to the sensorimotor cortex and underwent STN-DBS. Among them, 13 (81.3%) responded to the treatment, and two (12.5%) were seizure-free for at least 6 months. Three patients had Lennox-Gastaut syndrome (LGS)-like epilepsy and underwent CMN-DBS; all of them responded to the treatment (seizure frequency reductions: 51.6%, 79.6%, and 79.5%). Finally, one patient with bilateral occipital lobe epilepsy underwent PN-DBS, reducing the seizure frequency by 69.7%. Significance: ANT-DBS is effective for patients with TLE or ETLE. In addition, ANT-DBS is effective for patients with FBTCS. STN-DBS might be an optimal treatment for patients with motor seizures, especially when the EZ overlaps the sensorimotor cortex. CMN and PN may be considered modulating targets for patients with LGS-like epilepsy or occipital lobe epilepsy, respectively.

Ventral intermediate nucleus deep brain stimulation for treatment-resistant focal aware motor seizures: illustrative case.

BACKGROUND: Resection of the seizure onset zone (SOZ) is considered the gold standard for treating refractory focal aware seizures (FASs). When resective surgery is unadvisable, deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT; ANT-DBS) has been the procedure of choice. However, less than half of patients with FASs respond to ANT-DBS. The need for alternative targets to effectively treat FAS is thus evident. OBSERVATIONS: The authors report the case of a 39-year-old woman presenting with pharmaco-resistant focal aware motor seizures, with the SOZ located in the primary motor cortical area. She had previously undergone unsuccessful resection of the left temporoparietal operculum elsewhere. Considering the risk of new resective surgery, she was offered combined ventral intermediate nucleus (Vim)/ANT-DBS. Vim-DBS proved to be superior to ANT-DBS for seizure control (88% vs 32%), although the association of both provided the best results (97%). LESSONS: This is the first report on the use of the Vim as a target of DBS for the treatment of FAS. The excellent results were presumably obtained by modulation of the SOZ through Vim projections to the motor cortex. This opens a completely new avenue for treating FAS: chronic stimulation of specific thalamic nuclei.

The laterodorsal tegmentum and seizure regulation: Revisiting the evidence.

Electrical deep brain stimulation (DBS) is now a routine treatment option for patients suffering from medically refractory epilepsy. DBS of the anterior nucleus of the thalamus (ANT) has proven to be effective but, despite its success, few patients experience complete cessation of seizure activity. However, improving the therapy is challenging because the mechanism underlying its action remains largely unknown. One angle on improving the effectiveness of ANT stimulation is to better understand the various anatomic regions that send projections to and through this area. Here, the authors utilized a connectomic atlas of the mouse brain to better understand the regions projecting to the ANT and were particularly interested by the presence of robust cholinergic projections from the laterodorsal tegmentum (LDT). A subsequent review of the literature resulted in limited studies, which presented convincing evidence supporting this region's role in seizure control present in acute rodent models of epilepsy. It is thus the purpose of this paper to encourage further research into the role of the LDT on seizure mitigation, with mechanistic effects likely stemming from its cholinergic projections to the ANT. While previous studies have laid a firm foundation supporting the role of this region in modulation of seizure activity, modern scientific methodology has yet to be applied to further elucidate the mechanisms and potential benefits associated with LDT stimulation in the epileptic population.

Role of anterior thalamic circuitry during sleep.

Increased attention has been paid to the structure and function of anterior nucleus of the thalamus (ANT), since deep brain stimulation (DBS) treatment for epilepsy launched a decade ago. The efficacy of the treatment on seizure count varies patient from patient and we have limited information on the predictors of better outcomes. While the thalamus is considered the key brain region responsible for maintaining sleep, ANT was traditionally not involved in this function. Recent experimental and human data point to a possible role of ANT in sleep processes, although the underlying mechanisms are still ambiguous. Beside evaluating the current knowledge on sleep disturbances experienced during ANT-DBS treatment, the search for valid biomarkers primarily resides on a better understanding of sleep circuits implicating ANT and its subnuclei. Hypothetically better selectivity within the target may increase seizure outcomes and reduce psychiatric and cognitive side effects. Hence, the main scope of this review is to summarize the evidence on the activity measured in the ANT during non-REM and REM sleep. Furthermore, we aim to find shared properties of sleep processes and ANT-related functions examined more thoroughly during wakefulness, such as selective attention and memory.

Analysis of power spectrum and phase lag index changes following deep brain stimulation of the anterior nucleus of the thalamus in patients with drug-resistant epilepsy: A retrospective study.

OBJECTIVES: The mechanisms underlying the anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) for the treatment of drug-resistant epilepsy (DRE) have not been fully explored. The present study aimed to measure the changes in whole-brain activity generated by ANT DBS using interictal electroencephalography (EEG). MATERIALS AND METHODS: Interictal EEG signals were retrospectively collected in 20 DRE patients who underwent ANT DBS surgery. Patients were classified as responders or non-responders depending on their response to ANT DBS treatment. The power spectrum (PS) and Phase Lag Index (PLI) were determined and data analyzed using a paired sample t-test to evaluate activity differences between pre-and-post-treatment on different frequency categories. Student's t-test, Mann-Whitney test (non-parametric test) and Fisher exact test were used to compare groups in terms of clinical variables and EEG metrics. P values < 0.05 were considered statistically significant, and FDR-corrected values were used for multiple testing. RESULTS: PS analysis revealed that whole-brain spectral power had a significant decrease in the beta (p = 0.005) and gamma (p = 0.037) bands following ANT DBS treatment in responders. The analysis of scalp topographic images of all patients showed that ANT DBS decreases PS in the beta band at the F3, F7 and Cz electrode sites. The findings indicated a decrease in PS in the gamma band at the Fp2, F3, Cz, T3, T5 and Oz electrode sites. After ANT DBS treatment, PLI analysis showed a significant decrease in PLI between Fp1 and T3 in the gamma band in responders. CONCLUSION: The findings showed that ANT DBS induces a decrease in power in the left frontal lobe, left temporal lobe and midline areas in the beta and gamma bands. Lower whole-brain power in the beta and gamma bands can be used as biomarkers for a favorable therapeutic response to ANT DBS, and decreased synchronization between the left frontal pole and temporal lobe in the gamma band can also be used as a biomarker for effective clinical stimulation to guide postoperative programming.

Anterior Nucleus of the Thalamus Deep Brain Stimulation with Concomitant Vagus Nerve Stimulation for Drug-Resistant Epilepsy.

BACKGROUND: The Food and Drug Administration approved the deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) as an adjunctive therapy for drug-resistant epilepsy (DRE) in the United States in 2018. The DBS Therapy for Epilepsy Post-Approval Study is further evaluating the safety and effectiveness of ANT-DBS among different patients' groups. For this study, devices for vagus nerve stimulation (VNS) must be removed prior to enrolment. OBJECTIVE: To investigate the outcomes of concomitant ANT-DBS and VNS treatment for DRE. METHODS: A retrospective analysis was performed for 33 patients who underwent ANT-DBS using previous VNS to define distinct subgroups: standard ANT-DBS (9 subjects), ANT-DBS with functional VNS (12 subjects), and ANT-DBS with the VNS implantable pulse generator explanted or turned off at the time of the DBS (12 subjects). Effectiveness and safety data were analyzed across the whole population and among subgroups. RESULTS: A mean decrease in seizure frequency of 55% was observed after a mean follow-up of 25.5 mo. Approximately 67% of patients experienced ≥50% reduction in seizure frequency. Seizure reduction percentage was not significantly different among groups. Approximately 50% of subjects with no appreciable improvement and 75% of those who showed benefit after VNS (including improvement in seizure frequency, seizure severity, and seizure duration or quality of life) achieved a seizure reduction ≥50% after ANT-DBS surgery. There were no complications related to concomitant VNS and ANT-DBS. CONCLUSION: ANT-DBS for DRE provides excellent results despite previous and ongoing VNS therapy. Removal of VNS does not appear to be necessary before ANT-DBS.

Direct Targeting of the Anterior Nucleus of the Thalamus via 3 T Quantitative Susceptibility Mapping.

Objective: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is a potentially effective, minimally invasive, and reversible method for treating epilepsy. The goal of this study was to explore whether 3 T quantitative susceptibility mapping (QSM) could delineate the ANT from surrounding structures, which is important for the direct targeting of DBS surgery. Methods: We obtained 3 T QSM, T1-weighted (T1w), and T2-weighted (T2w) images from 11 patients with Parkinson's disease or dystonia who received subthalamic nucleus (STN) or globus pallidus interna (GPi) DBS surgery in our center. The ANT and its surrounding white matter structures on QSM were compared with available atlases. The contrast-to-noise ratios (CNRs) of ANT relative to the external medullary lamina (eml) were compared across the three imaging modalities. Additionally, the morphology and location of the ANT were depicted in the anterior commissure (AC)-posterior commissure (PC)-based system. Results: ANT can be clearly distinguished from the surrounding white matter laminas and appeared hyperintense on QSM. The CNRs of the ANT-eml on QSM, T1w, and T2w images were 10.20 ± 4.23, 1.71 ± 1.03, and 1.35 ± 0.70, respectively. One-way analysis of variance (ANOVA) indicated significant differences in CNRs among QSM, T1w, and T2w imaging modalities [F(2) = 85.28, p < 0.0001]. In addition, both the morphology and location of the ANT were highly variable between patients in the AC-PC-based system. Conclusion: The potential utility of QSM for the visualization of ANTs in clinical imaging is promising and may be suitable for targeting the ANT for DBS to treat epilepsy.

Deep brain stimulation in patients with long history of drug resistant epilepsy and poor functional status: Outcomes based on the different targets.

BACKGROUND: Deep brain stimulation (DBS) is a widely used surgical procedure for the treatment of patients with drug resistant epilepsy (DRE) and several anatomical target have been described. Indications for DBS includes patients with focal, partial seizure and those for which resective or disconnective surgery are contraindicated, such as involvement of eloquent cortex or significant comorbidities. Despite the SANTE trial has clearly indicated the efficacy of DBS of anterior nucleus of the thalamus (ANT), specific indications regarding the best anatomical target and outcome in patients with severe disability are lacking. Here we described our case series of patients underwent DBS of three different target including ANT, centromedian thalamic nucleus (CMN) and subthalamic nucleus (STN). METHOD: Six patients with DRE have been treated with DBS of ANT (n = 3), STN (n = 2) and CMN (n = 1). Outcome has been expressed as seizures frequency reduction and patients functional status after surgery with a follow-up of 5-11 years. RESULTS: Four out of six patients show no reduction of seizures frequency after DBS implant with one case of increasing atypical absence. Two cases, one ANT and one CMN, show a significant reduction of seizures frequency of 50-60%. No patients improve relative to functional outcome and one showed psychiatric symptoms worsening. CONCLUSIONS: For patients with DRE and severe functional disability, DBS may reduce seizure frequency in some cases, but it does not improve functional outcome.

Analysis of Deep Brain Stimulation Lead Targeting in the Stimulation of Anterior Nucleus of the Thalamus for Epilepsy Clinical Trial.

BACKGROUND: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an effective therapy for patients with drug-resistant focal epilepsy. Best practices for surgical targeting of the ANT can be refined as new information becomes available regarding effective stimulation sites. OBJECTIVE: To conduct a retrospective analysis of the relationship between outcomes (seizure reduction during year 1) and DBS lead locations in subjects from the SANTÉ pivotal trial (Stimulation of ANT for Epilepsy) based upon recent clinical findings. METHODS: Postoperative images from SANTÉ subjects (n = 101) were evaluated with respect to lead trajectory relative to defined anatomic landmarks. A qualitative scoring system was used to rate each lead placement for proximity to an identified target region above the junction of the mammillothalamic tract with the ANT. Each subject was assigned a bilateral lead placement score, and these scores were then compared to clinical outcomes. RESULTS: Approximately 70% of subjects had "good" bilateral lead placements based upon location with respect to the defined target. These subjects had a much higher probability of being a clinical responder (>50% seizure reduction) than those with scores reflecting suboptimal lead placements (43.5% vs 21.9%, P < .05). CONCLUSION: Consistent with experience from more established DBS indications, our findings and other recent reports suggest that there may be specific sites within the ANT that are associated with superior clinical outcomes. It will be important to continue to evaluate these relationships and the evolution of other clinical practices (eg, programming) to further optimize this therapy.

Deep Brain Stimulation for Treatment of Refractory Epilepsy.

BACKGROUND AND INTRODUCTION: Deep brain stimulation (DBS) has been increasingly used in the treatment of refractory epilepsy with remarkable safety. Experimental data demonstrated that electric current could modulate distinct brain circuits and decrease neuronal hypersynchronization seen in epileptic activity. The ability to carefully choose the most suitable anatomical target and precisely implant the lead is of extreme importance for satisfactory outcomes. OBJECTIVE: This video aimed to explore the targeting of the three most relevant nuclei in the treatment of refractory epilepsy. TECHNIQUE: Through a step-by-step approach, this video describes the surgical planning for DBS implantation in the anterior nucleus of the thalamus (ANT), the centromedian nucleus of the thalamus (CM), and the hippocampus (HIP). CONCLUSION: Each of the discussed targets has its own pearls and pitfalls that should be considered for an adequate lead placement. Accurate planning of the surgical procedure is essential for achieving optimal results.