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Objective: Short-term outcomes of deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) were reported for people with drug-resistant focal epilepsy (PwE). Because long-term data are still scarce, the Medtronic Registry for Epilepsy (MORE) evaluated clinical routine application of ANT-DBS., Methods: In this multicenter registry, PwE with ANT-DBS were followed up for safety, efficacy, and battery longevity. Follow-up ended after 5 years or upon study closure. Clinical characteristics and stimulation settings were compared between PwE with no benefit, improvers, and responders, that is, PwE with average monthly seizure frequency reduction rates of ≥50%., Results: Of 170 eligible PwE, 104, 62, and 49 completed the 3-, 4-, and 5-year follow-up, respectively. Most discontinuations (68%) were due to planned study closure as follow-up beyond 2 years was optional. The 5-year follow-up cohort had a median seizure frequency reduction from 16 per month at baseline to 7.9 per month at 5-year follow-up (p < .001), with most-pronounced effects on focal-to-bilateral tonic-clonic seizures (n = 15, 77% reduction, p = .008). At last follow-up (median 3.5 years), 41% (69/170) of PwE were responders. Unifocal epilepsy (p = .035) and a negative history of epilepsy surgery (p = .002) were associated with larger average monthly seizure frequency reductions. Stimulation settings did not differ between response groups. In 179 implanted PwE, DBS-related adverse events (AEs, n = 225) and serious AEs (n = 75) included deterioration in epilepsy or seizure frequency/severity/type (33; 14 serious), memory/cognitive impairment (29; 3 serious), and depression (13; 4 serious). Five deaths occurred (none were ANT-DBS related). Most AEs (76.3%) manifested within the first 2 years after implantation. Activa PC depletion (n = 37) occurred on average after 45 months., Significance: MORE provides further evidence for the long-term application of ANT-DBS in clinical routine practice. Although clinical benefits increased over time, side effects occurred mainly during the first 2 years. Identified outcome modifiers can help inform PwE selection and management., (© 2024 Medtronic and The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background and Objectives: The efficacy of deep brain stimulation of the anterior nucleus of the thalamus (ANT DBS) in patients with drug-resistant epilepsy (DRE) was demonstrated in the double-blind Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy randomized controlled trial. The Medtronic Registry for Epilepsy (MORE) aims to understand the safety and longer-term effectiveness of ANT DBS therapy in routine clinical practice., Methods: MORE is an observational registry collecting prospective and retrospective clinical data. Participants were at least 18 years old, with focal DRE recruited across 25 centers from 13 countries. They were followed for at least 2 years in terms of seizure frequency (SF), responder rate (RR), health-related quality of life (Quality of Life in Epilepsy Inventory 31), depression, and safety outcomes., Results: Of the 191 patients recruited, 170 (mean [SD] age of 35.6 [10.7] years, 43% female) were implanted with DBS therapy and met all eligibility criteria. At baseline, 38% of patients reported cognitive impairment. The median monthly SF decreased by 33.1% from 15.8 at baseline to 8.8 at 2 years ( p < 0.0001) with 32.3% RR. In the subgroup of 47 patients who completed 5 years of follow-up, the median monthly SF decreased by 55.1% from 16 at baseline to 7.9 at 5 years ( p < 0.0001) with 53.2% RR. High-volume centers (>10 implantations) had 42.8% reduction in median monthly SF by 2 years in comparison with 25.8% in low-volume center. In patients with cognitive impairment, the reduction in median monthly SF was 26.0% by 2 years compared with 36.1% in patients without cognitive impairment. The most frequently reported adverse events were changes (e.g., increased frequency/severity) in seizure (16%), memory impairment (patient-reported complaint, 15%), depressive mood (patient-reported complaint, 13%), and epilepsy (12%). One definite sudden unexpected death in epilepsy case was reported., Discussion: The MORE registry supports the effectiveness and safety of ANT DBS therapy in a real-world setting in the 2 years following implantation., Classification of Evidence: This study provides Class IV evidence that ANT DBS reduces the frequency of seizures in patients with drug-resistant focal epilepsy., Trial Registration Information: MORE ClinicalTrials.gov Identifier: NCT01521754, first posted on January 31, 2012., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Introduction: Deep brain stimulation of the anterior nucleus of thalamus (ANT-DBS) is an approved procedure for drug-resistant epilepsy. However, the preferred location inside ANT is not well known. In this study, we investigated the relationship between stereotactical coordinates of stimulated contacts and clinical improvement, in order to define the ideal target for ANT-DBS., Methods: Individual contact's coordinates were obtained in the Montreal Neurological Institute (MNI) 152 space, with the utilization of advanced normalization tools and co-registration of pre- and postoperative MRI and CT images in open-source toolbox lead-DBS with the "Atlas of the Human Thalamus." Each contact's pair was either classified as a responder (≥50% seizure reduction and absence of intolerable adverse effects) or nonresponder, with a minimum follow-up of 11 continuous months of stimulation., Results: A total of 19 contacts' pairs were tested in 14 patients. The responder rate was 9 out of 14 patients (64.3%). In 4 patients, a change in contacts' pairs was needed to achieve this result. A highly encouraging location inside ANT (HELIA) was delimited in MNI space, corresponding to an area in the anterior and inferior portion of the anteroventral (AV) nucleus, medially to the endpoint of the mammillothalamic tract (ANT-mtt junction) (x [3.8; 5.85], y [-2.1; -6.35] and z [6.2; 10.1] in MNI space). Statistically significant difference was observed between responders and nonresponders, in terms of the number of coordinates inside this volume. Seven responders and two nonresponders had at least 5 of 6 coordinates (2 electrodes) inside HELIA (77.8% sensitivity and 80% specificity). In 3 patients, changing to contacts that were better placed inside HELIA changed the status from nonresponder to responder., Conclusions: A relationship between stimulated contacts' coordinates and responder status was observed in drug-resistant epilepsy. The possibility to target different locations inside HELIA may help surpass anatomical variations and eventually obtain increased clinical benefit., (© 2021 S. Karger AG, Basel.)

Subcortical band heterotopia is a neuronal migration disorder that may cause refractory epilepsy. In these patients, resective surgery has yielded inadequate results. Deep brain stimulation of the anterior nuclei of the thalamus has been used for the treatment of refractory epilepsy with good results. We describe the first two patients with subcortical band heterotopia who were submitted to deep brain stimulation of the anterior nuclei of the thalamus, with evaluation of seizure outcome after 12 and 18 months of follow-up. At these times, both showed a >50% decrease in seizure frequency and an increase in seizure freedom. Both patients had a depressive syndrome after surgery that responded fully to anti-depressive medication in one patient and partly in the other. In both, deep brain stimulation of the anterior nuclei of the thalamus was associated with good seizure outcome. This procedure can therefore be considered in the treatment of patients with subcortical band heterotopia and refractory epilepsy. Depression may be a transient adverse event of the surgery or stimulation, however, its aetiology is probably multifactorial.

Introduction: Circadian rhythms (CRs) orchestrate intrinsic 24-hour oscillations which synchronize an organism's physiology and behaviour with respect to daily cycles. CR disruptions have been linked to Parkinson's Disease (PD), the second most prevalent neurodegenerative disorder globally, and are associated to several PD-symptoms such as sleep disturbances. Studying molecular changes of CR offers a potential avenue for unravelling novel insights into the PD progression, symptoms, and can be further used for optimization of treatment strategies. Yet, a comprehensive characterization of the alterations at the molecular expression level for core-clock and clock-controlled genes in PD is still missing. Methods and analysis: The proposed study protocol will be used to characterize expression profiles of circadian genes obtained from saliva samples in PD patients and controls. For this purpose, 20 healthy controls and 70 PD patients will be recruited. Data from clinical assessment, questionnaires, actigraphy tracking and polysomnography will be collected and clinical evaluations will be repeated as a follow-up in one-year time. We plan to carry out sub-group analyses considering several clinical factors (e.g., biological sex, treatment dosages, or fluctuation of symptoms), and to correlate reflected changes in CR of measured genes with distinct PD phenotypes (diffuse malignant and mild/motor-predominant). Additionally, using NanoStringⓇ multiplex technology on a subset of samples, we aim to further explore potential CR alterations in hundreds of genes involved in neuropathology pathways. Discussion: CLOCK4PD is a mono-centric, non-interventional observational study aiming at the molecular characterization of CR alterations in PD. We further plan to determine physiological modifications in sleep and activity patterns, and clinical factors correlating with the observed CR changes. Our study may provide valuable insights into the intricate interplay between CR and PD with a potential to be used as a predictor of circadian alterations reflecting distinct disease phenotypes, symptoms, and progression outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Patients with a neuronal migration disordered characterized by subcortical band heterotopia are prone to develop refractory epilepsy. Some attempts have been made to treat this condition surgically with Stereo-EEG and focal resections with discouraging results. In our series of deep brain stimulation of anterior nuclei of the thalamus (DBS-ANT), from 12 patients, 2 were due to this development disorder. Case Study: Seizure outcome was reviewed now at 12 and 18 months en patient 1 and 2. Both patients showed a greater than 50% decrease in seizure frequency and an increase in seizure free time. After surgery they both had a transient depressive syndrome that responded to anti-depressive medication. Discussion: Deep brain stimulation of ANT has shown a good seizure outcome in these two cases. We propose that this procedure could be considered in the treatment of patients with subcortical band heterotopia with refractory epilepsy. The etiology of depression is probably multifactorial but might be a transient adverse event of DBS-ANT. [ABSTRACT FROM AUTHOR]

Introduction: Deep Brain Stimulation (DBS) of the Anterior Nuclei of Thalami (ANT) has a growing interest as a palliative surgery for refractory epilepsy. The bilateral ANT-DBS may have a place in focal epilepsies when no focal resection is indicated or when patients refuse resective surgery. Material and Methods: The Epilepsy Surgery Group of the Hospital de Santa Maria (CHLN) started this approach in January 2011, and we have operated 12 patients (7 females) so far. Median time of epilepsy before implantation was 26 years (7-46) and median number of seizures per month 15 seizures/month (3-39). All patients have already tried 3 or more antiepileptic drugs. Three patients had previous epilepsy surgeries, one a VNS and other two resective surgeries. Electrodes were implanted with Leksell® stereotactic frame with targets and trajectories obtained from FrameLink® Medtronic's software. Both 3387 and 3389 electrodes were used through a trans-ventricular cannulated approach in the majority of the patients (9/12). Post-operative control of electrode contacts was done with CT fused with pre-operative MRI and compared to published stereotactic atlases. Results: All 12 patients have at least one contact in one ANT and 11 in both anterior nuclei. Two patients required additional surgeries due to slippage of electrode(s) to the III ventricle during a trans-ventricular approach. No intraventricular bleeding was seen in post-operative CT of all patients and no major complications related to surgery were recorded. Seizure frequency reduction was seen in more than half of the patients but almost all reported a decrease in severity of their seizures. Approximately one third of the patients developed a newly or aggravated depression early after stimulation initiation that required medication. No suicidal ideation was found in any of them. Discussion and Conclusions: The ideal candidates for ANT-DBS is yet to be found but the low incidence of major complications from this surgery and the reversibility of those related to stimulation makes this neuromodulation technique an option to treat otherwise difficult refractory epilepsy cases. Multicenter studies allow us to collect more cases faster but single center series with their more standardized approach may also add some important information. [ABSTRACT FROM AUTHOR]